Breast cancer is a world health problem and is a leading cause of cancer-related death among women in the United States. However, breast cancer risks were reported to be reduced through exposure to Vitamin D through its Receptors identified as the p53 target gene. The purpose of this study was to assess the associations between VDR gene polymorphisms knowledge/awareness and decisions to reduce breast cancer risks and likelihood of mammogram screening among women in Texas. Data from survey were used. Roy adaptation model was the theoretical framework that guided this quasi- experimental, quantitative research. The dependent variables were decisions to reduce breast cancer risks and likelihood of mammogram screening. The independent variables were knowledge about VDR gene polymorphisms and exposure to vitamin D. The covariates were level of education, awareness, lifestyle, breast self-exams, mammograms, age, early menarche, late menopause, and family history of breast cancer. The chi-square test and regression analysis were used to test the stated research hypotheses and to answer the research questions. Knowledge of VDR gene polymorphisms and exposure to vitamin D were not significantly associated with breast cancer risk, ï?£2 (3, N= 250) =3.84, p > 0.05. Also, awareness of the risk factors for breast cancer was not significantly associated with decisions to go for mammogram screenings or to enroll in breast cancer risk-reduction programs, ï?£2 (3, N= 250) =1.58, p > 0.05. To advocate for the promotion of awareness of the importance of pharmacogenetic testing for VDR gene polymorphisms for early detection of breast cancer, which would help to undertake appropriate therapeutic measures in a timely manner to prevent cancer metastasis, further research is warranted.

Η στεφανιαία νόσος αποτελεί ένα από τα πιο συχνά αίτια νοσηρότητας και θνητότητας στο γενικό πληθυσμό. Ένα μεγάλο ποσοστό από τους ασθενείς με στεφανιαία νόσο οδηγείται σε αγγειοπλαστική στεφανιαίων αρτηριών (PTCA) με ή χωρίς εμφύτευση stent, όταν η στένωση στο αγγείο είναι ≥ 70-75%. Παρά την πρόοδο στον τομέα της αγγειοπλαστικής, με τη χρήση των drug-eluting stents και την ελάττωση της επαναστένωσης σε ποσοστό <5-10%, το υψηλό ποσοστό (20-25%) επαναστένωσης παραμένει η Αχίλλειος πτέρνα στα συμβατικά, μεταλλικά(bare)stents. Η χρήση των drug-eluting stents περιορίζεται σε περιπτώσεις με επαναστένωση, σε σακχαροδιαβητικούς και σε υψηλού κινδύνου βλάβες για επαναστένωση. Τα μεγάλα ποσοστά όψιμης επαναστένωσης(≥ 9-10%) και το υψηλό κόστος τους, κάνουν ακόμα πιο επιτακτική την ανάγκη εντατικοποίησης της έρευνας προς την κατεύθυνση εντοπισμού παραγόντων σχετιζόμενων με την επαναστένωση. Σκοπός της εργασίας μας ήταν να διερευνήσει τον πιθανό ρόλο πολυμορφισμών γονιδίων στην υποτροπή ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών και εμφύτευση μεταλλικών stents. Συγκεκριμένα, εξετάσθηκε αναλυτικά ο γενετικός πολυμορφισμός των γονιδίων α2Β-αδρενεργικού υποδοχέα και της CETP(πρωτεΐνη μεταφοράς εστέρων χοληστερόλης). Η υπόθεση στηρίχτηκε στο γεγονός ότι σε μια σημαντική μελέτη 912 αρρένων Φινλανδών μέσης ηλικίας, αποδείχτηκε ότι ο D/D γονότυπος σε σχέση με τον I/D γονότυπο και τον I/I γονότυπο, εμφανίζει 2,5 φορές μεγαλύτερο κίνδυνο για οξέα στεφανιαία επεισόδια, συμπεριλαμβανομένου του εμφράγματος μυοκαρδίου. Η εκσεσημασμένη αγγειοσύσπαση, τόσο στην περιφέρεια, όσο και στις στεφανιαίες αρτηρίες μέσω του πολυμορφισμού του γονιδίου α2Β που θεωρείται πιθανό αίτιο για τα οξέα στεφανιαία επεισόδια, μαζί με το σημαντικό ρόλο του α2Β αδρενεργικού υποδοχέα στην υπερπλασία και μετανάστευση των λείων μυϊκών κυττάρων, πιθανόν να έχει μεγάλη συμβολή στη διεργασία της υποτροπής ισχαιμίας. Μελετήσαμε προοπτικά 96 Έλληνες που υπέστησαν επιτυχή PTCA και εμφύτευση stents, εκ των οποίων 81 ήταν άνδρες και 15 γυναίκες(μέση ηλικία ± σταθερά απόκλιση=57,7± 10,1 ετών, με όρια 37-76 ετών) που προσήλθαν με συμπτωματική στεφανιαία νόσο. Όλοι οι παραπάνω ασθενείς συμμετείχαν στη μελέτη μεταξύ των ετών 2001 και 2003 και παρακολουθήθηκαν κλινικά για 6-8 μήνες μετά από μια επιτυχή τεχνική διάνοιξης του αποφραγμένου αγγείου. Αμέσως μετά την PTCA και για ένα(1) μήνα οι ασθενείς έλαβαν ασπιρίνη(100-325mg/day) και κλοπιδογρέλη 75mg/day. Η εκτίμηση της υποτροπής ισχαιμίας βασίστηκε σε στατικό και δυναμικό σπινθηρoγράφημα θαλλίου στους 3 και 6-8 μήνες μετά την PTCA. Αιμοδυναμικά, σε όσους υπέστησαν νέα στεφανιογραφία μέχρι και τους 6-8 μήνες, η επαναστένωση ορίσθηκε ως ≥ 50% στένωση του αυλού του αγγείου στο σημείο όπου έγινε η αγγειοπλαστική. Εκτός από την ομάδα των ασθενών και μια ομάδα υγιών μαρτύρων 83 ατόμων, συμμετείχε στη μελέτη για σύγκριση της συχνότητας του γονότυπου. Το τελικό καταληκτικό σημείο για την παραπάνω μελέτη, ήταν η συχνότητα της υποτροπής ισχαιμίας στους 8 μήνες κλινικής παρακολούθησης. Υποτροπή ισχαιμίας και της επαναστένωσης ≥ 50% σε όσους υπεβλήθησαν σε νέα στεφανιογραφία, συνέβη σε 15 από τους 96 ασθενείς. Ας σημειωθεί ότι οι περισσότεροι ασθενείς (70/96) είχαν το φυσιολογικό γονότυπο με το αλληλόμορφο I, λιγότεροι ασθενείς (23/96) είχαν το Insertion/Deletion και μόλις 3/96 είχαν το Deletion/ Deletion γονότυπο. Από το γονοτυπικό group, υποτροπή ισχαιμίας παρουσιάσθηκε σε 11/70 για τον I/I, 3/23 για τον I/D γονότυπο και 1/3 για τον D/D γονότυπο. Δε βρέθηκε συσχέτιση μεταξύ πολυμορφισμού γονιδίου και υποτροπής ισχαιμίας στους ασθενείς μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Προηγούμενες μελέτες έχουν ερευνήσει τη συσχέτιση των πολυμορφισμών των γονιδίων της ACE, του AT1 υποδοχέα της αγγειοτενσίνης II και της CETP με την επαναστένωση μετά από αγγειοπλαστική. Εντούτοις, καμιά μελέτη δεν πραγματοποιήθηκε που να συγκρίνει τον α2Β-AR πολυμορφισμό και την υποτροπή ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Όπως αρχικά αναφέρθηκε, ο γονότυπος α2Β ευνοεί τη μετανάστευση των αγγειακών SMCs, επηρεάζει τη λειτουργία του Α.Ν.Σ. και συσχετίζει το α2Β-AR αλληλόμορφο D deletion με οξέα στεφανιαία επεισόδια. Όλα τα παραπάνω στοιχεία μπορεί να δικαιολογούν το ρόλο του α2Β-AR πολυμορφισμού στην υποτροπή ισχαιμίας και πιθανόν την επαναστένωση μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Βέβαια, η αρνητική συσχέτιση των πολυμορφισμών του α2Β-AR και της CETP ΤaqIB με την υποτροπή ισχαιμίας μετά από αγγειοπλαστική, μπορεί να θεωρηθεί προκαταρκτική, δεδομένου ότι συμμετείχε σχετικά μικρός αριθμός ασθενών συγκριτικά με μεγάλες πληθυσμιακές μελέτες και επειδή ο D/D γονότυπος δεν είναι ιδιαίτερα συχνός(για τη μελέτη των α2Β-AR). Όσον αφορά τη μελέτη με τη CETP, διερευνήσαμε τον πολυμορφισμό ΤaqIB που είναι μια σιωπηρή μετάλλαξη βάσης στο 277 νουκλεοτίδιο της CETP(η οποία μπορεί να αναγνωρισθεί με την περιοριστική ενδονουκλεάση ΤaqI), με την πιθανότητα υποτροπής ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Οι όροι Β1 και Β2 αντίστοιχα χρησιμοποιήθηκαν για να δηλώσουν την ύπαρξη ή μη της περιοριστικής περιοχής (site) της ΤaqIB. Το Β2 αλληλόμορφο σχετίζεται με αυξημένα επίπεδα HDL και ελαττωμένα επίπεδα CETP, τόσο σε υγιείς όσο και σε άτομα με στεφανιαία νόσο(μοιάζει με ήπιας μορφής ανεπάρκεια CETP). Αντίθετα το Β1 αλληλόμορφο σχετίζεται με ελαττωμένα επίπεδα HDL και με αυξημένα επίπεδα και δραστηριότητα CETP. Επειδή η ΤaqIB σχετίζεται με χαμηλά επίπεδα HDL και αυξημένο κίνδυνο για CHD(επηρεάζοντας το μεταβολισμό των λιποπρωτεϊνών), μπορεί να συμμετέχει στην παθοφυσιολογία της υποτροπής ισχαιμίας μετά από αγγειοπλαστική. Μελετήσαμε 204 ασθενείς από το έτος 2001 έως και το 2003 με την προοπτική να διερευνηθεί η συσχέτιση ΤaqIB στον Ελλαδικό πληθυσμό με την πιθανότητα υποτροπής ισχαιμίας μετά από αγγειοπλαστική σε άτομα που φέρουν τον παραπάνω γονότυπο. Η συχνότητα της ΤaqIB(54%) ήταν παρόμοια με τη συχνότητα του πολυμορφισμού σε μια ομάδα 35 υγιών μαρτύρων. Το αποτέλεσμα από αυτή τη μελέτη δεν αποδεικνύει ότι ο ΤaqIB πολυμορφισμός στο γονίδιο της CETP είναι σημαντικός προγνωστικός παράγων για εκτίμηση του κινδύνου υποτροπής ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Συμπερασματικά, η υποτροπή ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών οφείλεται σε έναν πολύπλοκο μηχανισμό και σε ένα πολυπαραγοντικό φαινόμενο. Μπορεί οι πολυμορφισμοί του α2Β και της CETP, να μην αναδείχθηκαν ως ανεξάρτητοι παράγοντες υποτροπής ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών, αλλά σε συνδυασμό με άλλους πολυμορφισμούς γονιδίων και υπό την επίδραση συγκεκριμένων περιβαλλοντικών παραγόντων, είναι πολύ πιθανόν να συμμετέχουν στην παραπάνω διεργασία της υποτροπής ισχαιμίας και κατ’επέκταση της επαναστένωσης μετά από PTCA. / Coronary heart disease is one of the most common causes of morbidity and mortality in the population. A great percent of the patients with coronary heart disease may undergo percutaneous coronary angioplasty (PTCA) with or without the implantation of stents, mainly when the stenosis of the vessel is ≥ 70-75%. Despite the progress made with the introduction of drug-eluting stents and the reduction of the restenosis rate up to 5%-10%, the Achillean heel of the angioplasty using bare metal stents, is the restenosis rate which is 20%-25% of all cases. The use of drug-eluting stents is limited in cases with restenosis, in patients with diabetes mellitus and in high-risk for restenosis lesions. The great percent of late restenosis(≥ 9-10%) and the high price of drug-eluting stents, make more urgent the necessity for more intense research on the identification of the exact factors involved in the pathophysiology of restenosis. The primary objective of our study is to define the role of gene polymorphisms in the recurrence of ischaemia after PTCA and the implantation of the stents. Virtually, we scrutinely examined the role of the genetic polymorhisms of α2Badrenergic receptor and the CETP(Cholesteryl Ester Transfer Protein)-TaqIB polymorphism. Our assumption was based on the conclusion drawn by a study conducted in Finnish patients, which showed that D/D genotype confers 2,5 increase in the risk for acute coronary events(including acute myocardial infarction). The intense vasoconstriction properties of the α2Badrenergic polymorphism both on the coronary arteries and the periphery is considered to be the primary cause of the acute coronary events. The aforementioned statement with the significant role of α2B adrenergic receptor α2B-AR on the hyperplasia and mainly the migration of smooth muscle cells, probably correlates well with the pathophysiology of the recurrence of ischaemia after PTCA. We conducted a genetic association/prospective follow-up study in 96 Greek coronary artery disease patients undergoing coronary angioplasty and stent implantation. 81 patients were men and 15 women(mean age ± standard deviation=57,7± 10,1 years, ranges 37-76 years old) who presented with symptomatic CAD. All patients were enrolled in the study between 2001 and 2003 and were followed-up clinically for 6-8 months after an initially successful procedure. Post-angioplasty and for one (1) month following the procedure, all the patients received aspirin(100-325mg/day) and clopidogrel(75mg/day). Assessment of recurrence of ischaemia was based on positive thallium stress testing(at least moderate defect to the distribution of the culprit lesion of the vessel which was revascularised). Hemodynamically, restenosis was defined as ≥50% narrowing of the vessel at the point where angioplasty was performed. In addition to the patient group, a control group of totally 83 asymptomatic individuals were included in the study for comparison of the frequency of the genotype. The final end-point of the current study was the incidence of restenosis at 8 months of clinical follow-up. Recurrence of ischaemia (including restenosis rate ≥50% to the patients who underwent coronary angiography) occurred in 15 of the 96 patients. In note, the majotiy of patients (70/96) had the Insertion/Insertion genotype, fewer patients (23/96) had the Insertion/Deletion genotype and only 3/96 had the Deletion /Deletion genotype. With regard to to the genotype groups , restenosis was found in 11/70 for I/I, 3/23 for I/D and 1/3 for the D/D genotype. No association between gene polymorphisms and recurrence of ischaemia was detected to the patients who underwent coronary angioplasty. Previous studies have investigated the association between gene polymorhisms of angiotensin-converting enzyme(ACE), the AT1 receptor for angiotensin II and cholesteryl ester transfer protein (CETP) with restenosis in patients after coronary angioplasty. However, no study has been performed to involve the α2B-AR polymorphism with recurrence of ischaemia after percutaneous angioplasty of coronary vessels. As it was initially mentioned, α2B genotype promotes the migration of vascular SMCs, influences the function of autonomic nervous system and the α2B-AR deletion variant is associated with acute coronary events. All these data might correlate the role of α2B-AR polymorphism with the recurrence of ischaemia and probably with the restenosis after an angioplasty of coronary vessels. Nevertheless, the negative findings of our study might be considered preliminary, taking into account the small number of patients that were studied and the rarity of the Deletion/Deletion(D/D) genotype. As far as the CETP study, we investigated the TaqIB polymorphism, which is a silent base change affecting the 277th nucleotide and can be identified by the restriction endonuclease TaqI, with the chance of recurrence of ischaemia after PTCA. The terms B1 and B2 are used to denote the presence and absence, respectively, of the TaqI restriction site. The B2 allele has been associated with increased HDL levels and decreased CETP levels and activity in both patients with CHD and healthy subjects(resembling a mild form of CETP deficiency). On the other hand, the B1 allele has been associated with decreased HDL levels and increased CETP levels and activity. Due to the fact that TaqIB is associated with decreased HDL levels and increased risk for CHD, affecting the lipoprotein metabolism might be involved in the pathophysiology of reccurence of ischaemia after PTCA. We studied 204 patients between 2001 and 2003 with the primary objective to investigate the frequency of TaqIB and possible association with reccurence of ischaemia after PTCA in the patients who have this genotype. The frequency of TaqIB was 54% similar to the frequency of the polymorphism in a group of 35 healthy controls. The results from this study does not indicate that the TaqIB polymorphism at the CETP gene locus is a significant predictor for assessing the risk of reccurence of ischaemia after PTCA. As a conclusion, reccurence of ischaemia after PTCA is due to a complicated mechanism and to a multifactoral phenomenon. Virtually, we didn’t find any correlation of α2ΒAR polymorphism and CETP TaqIB with reccurence of ischaemia, especially as causitive factors, but based on their role in the pathophysiology, under certain circumstances, especially with the cooperation of other genes, these polymorphisms can not be definitely excluded in the reccurence of ischaemia and the restenosis after PTCA.

Daktaro disertacijos „Nėštumo laukimo laiką prognozuojančių veiksnių tyrimas“ tikslas - įvertinti nėštumo laukimo laiko sąsajas su demografiniais, socialiniais, gyvensenos, darbo, aplinkos ir genetiniais veiksniais ir sudaryti prognostinius jų įtakos modelius. Tyrimo uždaviniai: 1.Įvertinti demografinių, socialinių, gyvensenos, darbo ir gyvena–mosios aplinkos veiksnių sąsajas su nėštumo laukimo laiku. 2.Sudaryti svarbiausių demografinių, socialinių, gyvensenos, darbo ir gyvenamosios aplinkos veiksnių, kurie nulemia 12 mėnesių ir ilgesnį nėštumo laukimo laiką, prognostinį įvertinimo modelį. 3.Įvertinti FSH receptoriaus geno polimorfizmo variantų įtaką nėš–tumo laukimo laikui. 4.Sudaryti FSH receptoriaus geno polimorfizmo įtakos svarbiausiems demografiniams, socialiniams, gyvensenos, darbo ir gyvenamosios aplinkos veiksniams, kurie nulemia 12 mėnesių ir ilgesnį nėštumo laukimo laiką, prognostinį modelį. Nustatėme, kad svarbiausi nepriklausomi 12 mėnesių ir ilgesnį nėštumo laukimo laiką nulemiantys prognostiniai veiksniai yra 30 metų ir vyresnis amžius, anksčiau gydyti vaisingumo sutrikimai, ginekologinės ligos, kontracepcijos priemonių naudojimas iki nėštumo planavimo pradžios ir FSH receptoriaus geno SER/SER variantas, kurie pastojimo po 12 ir daugiau mėnesių tikimybę didino, atitinkamai, 1,95, 1,57, 2,21, 1,87 ir 1,68 kartus. / “Study of time to pregnancy prognostic factors”. The aim of the study was to investigate the relation between various factors and female fecundity, which was expressed as time to pregnancy (TTP) and to create prognostic models. Tasks of the study were: 1.Estimate the relation between socioeconomic, demographic, life-style, environmental and job-related factors and time to pregnancy; 2.Create prognostic valuation model for the most important social, demographic, life-style, environmental and job-related factors what are associated with 12 month or longer time to pregnancy; 3.Estimate the impact of FSH receptor gene polymorphism variant on time to pregnancy; 4.Create prognostic model for the most important factors what are associated with 12 month or longer time to pregnancy under the influence of FSH receptor gene polymorphism. We established, that the most important independent risk factors prognoses time to pregnancy of 12 or more months in women analyzed for FSH receptor gene polymorphism group were older age, having gynecological diseases or fertility problems in the past, the use of contraception prior to conception and SER/SER polymorphism variant, what increased the probability of conceiving after 12 or more months 1.95, 1.57, 2.21, 1.87 and 1.68 times respectively.

To investigate the in vitro antioxidant properties of the ovulation induction drug, Citrate clomiphene (CC), and to access whether its effects are influenced by the Ala16Val polymorphism in the SOD2 gene, which encodes mitochondrial manganese superoxide dismutase (SOD), an in vitro experimental study testing the effect of different concentrations of CC on antioxidant capacity, reactive oxygen species (ROS) production and peripheral blood mononuclear cells (PBMC) culture viability was performed. A total of 58 healthy adult women were genotyped for the Ala16Val SOD2 polymorphism, and blood samples were collected to perform in vitro experiments analyzing the biological antioxidant effects of CC. Free radical production and cytotoxicity assays were performed on blood and peripheral blood mononuclear cells (PBMCs) with different Ala16Val SOD2 genotypes. According to the observations described here, CC exhibited antioxidant effects. Additionally, the CC treatments led to a decrease in ROS production, with blood samples from the AA genotype displaying a more responsive antioxidant effect from CC than other genotypes. AA and AV PBMCs showed an increase in viability following treatment with 10 μM CC when compared with PMBCs from control groups. In the VV PBMC group, only the 5 μM and 10 μM CC treatments presented a significant positive viability effect. The CC exhibits antioxidant activity, similar to that observed with other Selective Estrogen Receptor Modulators (SERMs), in the presence of the Ala16Val-SOD2 polymorphism suggesting pharmacogenetic effect. / Para investigar in vitro as propriedades antioxidantes de drogas que induzem a ovulação, como citrato de clomifeno (CC) e verificar se os efeitos são influenciados pelo polimorfismo Ala16Val do gene da SOD2, o qual codifica a superóxido dismutase (SOD) mitocondrial dependente de manganês. Um estudo experimental in vitro foi conduzido testando o efeito de diferentes concentrações de CC sobre a capacidade antioxidante, produção de espécies reativas de oxigênio (EROs) e na viabilidade de células mononucleadas de sangue periférico (CMSP) em cultura celular. Um total de 58 mulheres adultas saudáveis foram genotipadas para o polimorfismo Ala16Val do gene da SOD2, e sangue foi coletado para realizar os experimentos in vitro e analisar os efeitos antioxidantes biológicos do CC. A produção de radicais livres e análise de citotoxicidade foram conduzidas em sangue e CMSP com diferentes genótipos do Ala16Val SOD2. De acordo com as observações descritas aqui, o CC exibiu um efeito antioxidante. Adicionalmente, os tratamentos com CC levaram a um decréscimo na produção de EROs, com amostras de sangue o genótipo AA desenvolveu um efeito antioxidante mais responsivo para o CC do que os outros genótipos. A cultura de CMSP dos genótipos AA e AV mostraram um aumento na viabilidade seguida do tratamento com 10μM CC quando comparada com as culturas CMSP do grupo controle. No grupo de cultura CMSP do genótipo VV, somente os tratamentos com 5μM e 10μM de CC apresentaram efeito positivo na viabilidade. O CC apresentou uma atividade antioxidante similar à observada com outros moduladores seletivos dos receptores de estrogênio (SERMs). Entretanto, essa atividade foi influenciada pelos diferentes genótipos do polimorfismo Ala16Val SOD2 sugerindo efeito farmacogenético.

Introduction: Preeclampsia (PE) is characterized by the occurrence of gestational hypertension and proteinuria. Cytokines as IL-1 can cause an exaggerated inflammatory process causing oxidative stress and endothelial damage. In PE, and considering the ethnic variation, these cytokines are encoded through their encoding gene: among them the IL1B gene. Objectives: In order to investigate the association of polymorphisms in the IL1B gene in women with preeclampsia and the influence of possible maternal, environmental and genetic risk factors, a case-control study was conducted in two reference maternity hospitals in the state of Sergipe. Methods: An interview was done and the DNA of 456 volunteers collected for analysis. The predominance of melanoderma and feoderma individuals is emphasized here: few studies with this population are found in the literature regarding IL1B and PE. The genetic analysis aimed the representation of the gene integrally and for this purpose four tagSNPs for IL1B gene were analyzed: rs1143643, rs1143633, rs1143634 and rs1143630. The analysis of the association between the haplotypes and p values were calculated using the THESIAS software. Chi square test, Fisher test, Odds Ratio, confidence interval and multivariate logistic regression were performed. Results: Factors such as rs1143630 polimorphisms, obesity, primiparity, cesarean delivery and low level of consciousness at the time of admission to the health service were related to PE. Suggestive evidence of association between "T" allele in rs1143630 and preeclamptic women was observed. Conclusions: Clinical factors and IL1B polimorphisms were associated with severe preeclampsia. In many aspects, avoid maternal deaths related with preeclampsia is one of the most important and urgent challenges of obstetrics today. / Introdução: Pré-eclâmpsia (PE) é uma doença caracterizada pela ocorrência de hipertensão e proteinúria na gestação. Algumas citocinas como a IL-1 podem causar um processo inflamatório exagerado, causando lesão endotelial e estresse oxidativo. Na PE, e considerando-se a variação étnica, citocinas são codificadas através de seu gene codificador, entre eles o gene IL1B. Objetivos: Com o objetivo de investigar a associação entre polimorfismos no gene IL1B em mulheres com PE e a influência de possíveis fatores de risco maternos e ambientais, realizou-se um estudo do tipo caso-controle em duas maternidades de referência no estado de Sergipe. Métodos: Uma entrevista foi realizada e o DNA de 456 voluntárias foi coletado para análise. Ressalta-se aqui a predominância de indivíduos melanodermas e feodermas: poucos estudos com esta população são encontrados na literatura utilizando essa população em particular relacionando o gene IL1B e PE. A análise genética objetivou a representação do gene integralmente e para tanto quatro tagSNPs do gene IL1B foram analisados, sendo eles: rs1143643, rs1143633, rs1143634 e rs1143630. A análise da associação entre os haplótipos e valores de P foram calculados usando o software THESIAS. Teste de qui-quadrado, Teste de Fisher, Odds Ratio, intervalo de confiança e regressão logística foram realizados. Resultados: Fatores como polimorfismos do rs1143630, obesidade, primiparidade, parto cesáreo e baixo nível de consciência no momento da admissão no serviço de saúde relacionaram-se à PE. Foi identificada evidência sugestiva da associação do alelo “T” no rs1143630 no grupo de mulheres com PE. Conclusão: Fatores clínicos e polimorfismos do gene IL1B estiveram associados à ocorrência de pré-eclâmpsia. Em muitos aspectos, combater morte materna causada por pré-eclâmpsia é um dos desafios mais importantes e urgentes da obstetrícia na atualidade.

Introduction: Preeclampsia (PE) is characterized by the occurrence of gestational hypertension and proteinuria. Cytokines as IL-1 can cause an exaggerated inflammatory process causing oxidative stress and endothelial damage. In PE, and considering the ethnic variation, these cytokines are encoded through their encoding gene: among them the IL1B gene. Objectives: In order to investigate the association of polymorphisms in the IL1B gene in women with preeclampsia and the influence of possible maternal, environmental and genetic risk factors, a case-control study was conducted in two reference maternity hospitals in the state of Sergipe. Methods: An interview was done and the DNA of 456 volunteers collected for analysis. The predominance of melanoderma and feoderma individuals is emphasized here: few studies with this population are found in the literature regarding IL1B and PE. The genetic analysis aimed the representation of the gene integrally and for this purpose four tagSNPs for IL1B gene were analyzed: rs1143643, rs1143633, rs1143634 and rs1143630. The analysis of the association between the haplotypes and p values were calculated using the THESIAS software. Chi square test, Fisher test, Odds Ratio, confidence interval and multivariate logistic regression were performed. Results: Factors such as rs1143630 polimorphisms, obesity, primiparity, cesarean delivery and low level of consciousness at the time of admission to the health service were related to PE. Suggestive evidence of association between "T" allele in rs1143630 and preeclamptic women was observed. Conclusions: Clinical factors and IL1B polimorphisms were associated with severe preeclampsia. In many aspects, avoid maternal deaths related with preeclampsia is one of the most important and urgent challenges of obstetrics today. / Introdução: Pré-eclâmpsia (PE) é uma doença caracterizada pela ocorrência de hipertensão e proteinúria na gestação. Algumas citocinas como a IL-1 podem causar um processo inflamatório exagerado, causando lesão endotelial e estresse oxidativo. Na PE, e considerando-se a variação étnica, citocinas são codificadas através de seu gene codificador, entre eles o gene IL1B. Objetivos: Com o objetivo de investigar a associação entre polimorfismos no gene IL1B em mulheres com PE e a influência de possíveis fatores de risco maternos e ambientais, realizou-se um estudo do tipo caso-controle em duas maternidades de referência no estado de Sergipe. Métodos: Uma entrevista foi realizada e o DNA de 456 voluntárias foi coletado para análise. Ressalta-se aqui a predominância de indivíduos melanodermas e feodermas: poucos estudos com esta população são encontrados na literatura utilizando essa população em particular relacionando o gene IL1B e PE. A análise genética objetivou a representação do gene integralmente e para tanto quatro tagSNPs do gene IL1B foram analisados, sendo eles: rs1143643, rs1143633, rs1143634 e rs1143630. A análise da associação entre os haplótipos e valores de P foram calculados usando o software THESIAS. Teste de qui-quadrado, Teste de Fisher, Odds Ratio, intervalo de confiança e regressão logística foram realizados. Resultados: Fatores como polimorfismos do rs1143630, obesidade, primiparidade, parto cesáreo e baixo nível de consciência no momento da admissão no serviço de saúde relacionaram-se à PE. Foi identificada evidência sugestiva da associação do alelo “T” no rs1143630 no grupo de mulheres com PE. Conclusão: Fatores clínicos e polimorfismos do gene IL1B estiveram associados à ocorrência de pré-eclâmpsia. Em muitos aspectos, combater morte materna causada por pré-eclâmpsia é um dos desafios mais importantes e urgentes da obstetrícia na atualidade.

Submitted by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-24T13:05:15Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Gabrielle_Gastar.pdf: 1814034 bytes, checksum: 214de94beffb5c3d14f679611239db4b (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-24T13:56:54Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Gabrielle_Gastar.pdf: 1814034 bytes, checksum: 214de94beffb5c3d14f679611239db4b (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-24T13:57:01Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Gabrielle_Gastar.pdf: 1814034 bytes, checksum: 214de94beffb5c3d14f679611239db4b (MD5) / Made available in DSpace on 2018-05-24T13:57:01Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Gabrielle_Gastar.pdf: 1814034 bytes, checksum: 214de94beffb5c3d14f679611239db4b (MD5) Previous issue date: 2017-08-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / OBJETIVO: Estudar as associações entre os polimorfismos genéticos ECA I/D, ACTN3 R577X e PON1 C(-107)T com diabetes e hipertensão em pacientes atendidos pelo Sistema Único de Saúde. MÉTODOS: Foram coletados dados bioquímicos dos prontuários dos pacientes crônicos de três Unidades Básicas de Saúde da Família localizadas na cidade de Rio Grande. Foram aplicados questionários de consumo alimentar, nível de atividade física e socioeconômico. Foi realizada a avaliação nutricional dos pacientes e, em seguida, a coleta de saliva para a extração do DNA genômico para análise dos polimorfismos genéticos. Os polimorfismos foram analisados por PCR simples, multiplex e por polimorfismo de tamanho de fragmento de restrição. RESULTADOS: O grupo caso obteve maiores valores de peso, IMC, circunferência da cintura, percentual de gordura, pressão arterial, colesterol total, triglicerídeos e glicemia em comparação ao grupo controle. Foram encontradas associações do genótipo XX do polimorfismo R577X da ACTN3 com valores mais elevados de glicemia e triglicerídeos. O genótipo TT do polimorfismo C(-107)T da PON1 também obteve níveis maiores de triglicerídeos comparado aos outros 2 genótipos. CONCLUSÃO: O genótipo XX da ACTN3 foi fortemente relacionado com níveis baixos de HDL e altos valores de triglicerídeos, colesterol total e glicemia. Ainda encontramos altos valores de triglicerídeos e LDL no genótipo TT e menores níveis de colesterol total ligados ao genótipo CC da PON1. / OBJECTIVE: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 C-(107)T with chronic diseases (diabetes and hypertension) in patients attended by Sistema Único de Saúde (SUS). METHODS: Biochemical data were collected from the charts in the Basic Health Units of the Family located in the same region of the city of Rio Grande. Charts about food consumption, physical activity level and socioeconomic were applied. Nutritional data were evaluated, genomic DNA was extracted from collected saliva samples and used for analysis of genetic polymorphism. RESULTS: The case group had higher values of weight, BMI, waist circumference, body fat percentage, blood pressure, cholesterol, triglycerides and blood glucose in comparison with control group. Associations were found of XX genotype of the polymorphism R577X ACTN3 with higher values of blood glucose, and triglycerides levels. The TT genotype of the C(-107)T PON1 also had higher levels of triglycerides compared to other 2 genotypes. CONCLUSION: The genotype XX of ACTN3 was strong related with low HDL levels and high triglycerides, total cholesterol and glucose levels. Still, we realized high triglycerides and LDL leves in TT genotype of PON1 and lower leves of total cholesterol linked to CC genotype of PON1.

Abstract Respiratory distress syndrome, RDS, is a multifactorial lung disease of premature infants. The main cause of RDS is a deficiency of pulmonary surfactant, a lipoprotein mixture required to reduce surface tension at the air-liquid interface and to prevent generalized atelectasis of the alveolar ducts and alveoli. Prematurity is the most important factor predisposing to RDS. During the past decade the number of multiple pregnancies has increased significantly as a result of diversified infertility treatments and advanced maternal age. Due to the considerably higher rate of preterm births of multiples compared to singletons, RDS is one of the major causes of morbidity among them. The objectives of the present research were to evaluate the incidence and risk factors of RDS in twins compared to singletons, and to assess the role of SP-A and SP-B gene variations and gene-environment interactions in the susceptibility to the disease in a population of preterm twins and higher order multiples. This research showed that during the past fifteen years the gestational age-specific incidence of RDS has declined. Twin infants do not have increased risk of RDS except when born very immaturely at a very early gestational age. The presenting twin is less susceptible to RDS than the non-presenting twin or singleton infant after 28 weeks of gestation until term. Additionally the SP-B Ile131Thr polymorphism was shown to affect the susceptibility specifically in the presenting twin. The role of SP-A polymorphisms in the risk of RDS in twins turned out to be different from that in singletons. The major allele and genotype of SP-A1 were associated with a decreased risk of RDS in near-term twin infants. The threonine allele in SP-B Ile131Thr appeared interactively with SP-A1 to associate with the risk of RDS both in twins and in singletons: associating with a lower risk of RDS in singletons at very early gestation, but surprisingly associating with a protection in twins and multiples from RDS near term. The risk of RDS, defined by the interaction of SP-A and SP-B alleles, was additionally associated with the fetal mass. Thus, the difference in the susceptibility to RDS in premature singletons and multiples may depend on the size of the conceptus. In an evaluation of the genetic risk factors for RDS, the classical twin study method comparing the concordance of a disease between MZ and DZ twins underestimates the extent of heredity. Several predominant intrauterine and perinatal environmental factors contribute to disease susceptibility regardless of zygosity and are suspected to override the hereditary components of RDS. Twin gestation was shown to be an effect modifier in the genetic susceptibility to RDS. / Tiivistelmä Vastasyntyneen hengitysvaikeusoireyhtymä, RDS-tauti, on hyvin monitekijäinen ennenaikaisena syntyneiden lasten sairaus. Taudin tärkein syy on keuhkojen pintajännitystä alentavan aineen, surfaktantin, puute ennenaikaisessa synnytyksessä. Surfaktantti on rasva-proteiiniseos, joka alentaa keuhkorakkuloiden pintajännitystä ja estää rakkuloiden kasaan painumisen hengityksen aikana. Epäkypsyys on tärkein RDS-taudin kehittymiselle altistava tekijä. Viimeisen vuosikymmenen aikana monisikiöiset raskaudet ovat lisääntyneet merkittävästi keinohedelmöitysten ja synnyttäjien kohonneen iän seurauksena. RDS-tauti on monisikiösynnytyksissä tärkeä sairastavuutta aiheuttava tekijä, koska monisikiöraskaudet päättyvät huomattavasti useammin ennenaikaisesti kuin yksösraskaudet. Tämän tutkimuksen tarkoituksena oli selvittää RDS-taudin ilmaantuvuutta ja riskitekijöitä kaksosilla verrattuna yksösiin, tutkia surfaktanttiproteiinien A ja B geenivaihtelua sekä geenien ja ympäristötekijöiden vuorovaikutusta kaksosten ja monisikiöisistä raskauksista syntyneiden lasten RDS-taudissa. Tutkimus osoitti, että viimeisten viidentoista vuoden aikana RDS-taudin raskausikäkohtainen ilmaantuvuus on vähentynyt. Vain hyvin epäkypsillä, ennenaikaisilla kaksosilla on lisääntynyt riski sairastua RDS-tautiin verrattuna yksösiin. 28 raskausviikon jälkeen ensimmäisenä syntyvällä kaksosella on pienempi riski saada RDS-tauti kuin toisena syntyvällä tai yksösellä. Lisäksi surfaktanttiproteiini B:n (SP-B) geenin eksonin 4 monimuotoisuus osoittautui vaikuttavan RDS-taudin alttiuteen erityisesti ensin syntyvällä kaksosella. Surfaktanttiproteiini A:n (SP-A) geenin yhteys RDS-taudin riskiin osoittautui olevan erilainen kaksosilla verrattuna yksösiin. Lähes täysiaikaisilla kaksosilla SP-A1 geenin valta-alleeli ja genotyyppi liittyivät RDS-taudin vähentyneeseen riskiin. SP-B geenin eksonin 4 treoniini alleeli osoittautui liittyvän yhdessä SP-A1 valtagenotyypin kanssa RDS-taudin riskiin sekä yksösillä että kaksosilla: hyvin ennenaikaisilla yksösillä geenien yhteisvaikutus lisäsi riskiä, kun taas lähes täysiaikaisilla kaksosilla sama geenien yhteisvaikutus yllättäen suojeli RDS-taudilta. SP-A ja SP-B geenien vuorovaikutuksen kautta välittyvä RDS-taudin riski oli lisäksi yhteydessä sikiön kokoon. Siten ennenaikaisena syntyneiden yksösten ja monisikiöisten RDS-taudin alttiuden ero voi olla riippuvainen sikiön koosta. Klassinen kaksostutkimusmenetelmä, jossa verrataan identtisten ja ei-identtisten kaksosten sairastuvuutta, aliarvioi perimän määräämien tekijöiden osuutta RDS-taudin synnyssä. Useat hallitsevat kohdunsisäiset ja synnytykseen liittyvät ympäristötekijät vaikuttavat RDS-taudin syntyyn ja kumoavat perimän osuutta. Kaksosuus osoittautui olevan periytymisen vaikutusta muokkaava tekijä RDS-taudissa.

No description available.

O objetivo do presente estudo foi avaliar a associação entre lesões de cárie dentária e defeitos do desenvolvimento do esmalte (DDEs) com o índice de massa corporal e com polimorfismos nos genes que codificam as metaloproteinases 8, 13 e 20, em uma população de crianças amazônicas. A amostra foi constituída de 221 crianças, com idade entre 9 e 12 anos, de ambos os gêneros, matriculadas em quatro escolas públicas da cidade de Manaus - Amazonas. Durante o exame clínico foram obtidos os índices CPO-D e/ou ceo-d, dados referentes aos DDEs e dados antropométricos (peso e altura). Os responsáveis responderam a um questionário sobre hábitos de higiene bucal e dieta. Amostras de saliva foram coletadas como fonte de DNA genômico e, por meio do método Taqman, por PCR em tempo real, realizou-se a genotipagem das regiões rs17099443 e rs3765620 no gene que codifica a MMP8; rs478927 e rs2252070 no gene que codifica a MMP13; e rs1784418 no gene que codifica a MMP20. Os dados foram submetidos à análise estatística empregando os testes de Shapiro-Wilk, ANOVA, Tukey, Qui-quadrado, Exato de Fisher e a razão de chance, com nível de significância de 5%. De acordo com os resultados obtidos verificou-se que, nas crianças com baixo peso, a média de lesões de cárie dental foi 1,00 (DMP 1,00), nas eutróficas a média de lesões de cárie dental foi de 1,57 (DMP 2,00), nas com sobrepeso, a média foi de 1,44 (DMP 1,86) e nas crianças obesas foi de 3,12 (DMP 2,63). Crianças obesas apresentaram mais lesões de cárie que as crianças eutróficas e com sobrepeso (p<0,05). Nos genes que codificam MMP8, MMP13 e MMP20 os alelos polimórficos foram observados em maior frequência nos indivíduos com experiência de cárie, com associação significativa apenas para o polimorfismo rs478927 no gene que codifica a MMP13 (p=0,043). Com relação aos DDE, os alelos polimórficos foram observados em maior frequência nos genes que codificam MMP8, MMP13 e MMP20, com associação significativa apenas para o polimorfismo rs478927 no gene que codifica a MMP13 (p=0,005). Para o gene que codifica MMP13, houve diferença significativa na distribuição dos genótipos entre os grupos controle e DDE (p=0,017). Com base nos parâmetros analisados e nos resultados obtidos, foi possível concluir que, em crianças de Manaus-AM, as lesões de cárie estiveram associadas com obesidade, e que houve associação entre o polimorfismo genético (rs478927) no gene que codifica a MMP13 com presença de lesões de cárie e DDEs / The objective of the present study was to evaluate the association between dental caries lesions and developmental enamel defects (DED) with body mass index and polymorphisms in gene encoding matrix metalloproteinases 8, 13 and 20 in a population of Amazonian children. The sample consisted of 221 children, aged between 9 and 12 years, of both genders, regularly enrolled in four public schools in the city of Manaus, Amazonas State, Brazil. During the clinical examination, the researchers recorded DMFT and/or dmft indexes, DED data and anthropometric data (weight and height). Parents/caregivers answered a questionnaire about children´s oral hygiene habits and diet. Saliva samples were collected as a source of genomic DNA and, using TaqMan real-time PCR, genotyping was performed of regions rs17099443 and rs3765620 in the gene encoding MMP8; rs478927 and rs2252070 in the gene encoding MMP13; and rs1784418 in the gene encoding MMP20. Data were submitted to statistical analysis using the Shapiro-Wilk, ANOVA, Tukey, Qui-quadrado, Exato de Fisher and odds ratio tests, with a significance level of 5%. According to the results, it was found that, in children with low weight, the mean number of dental caries lesions was 1.00 (SD 1.00); in the eutrophic children the mean was 1.57 (SD 2.00); in the overweight children, the mean was 1.44 (SD 1.86) and in obese children the mean was 3.12 (SD 2.63). Obese children had more dental caries lesions than eutrophic and overweight children (p<0.05). In the genes encoding MMP8, MMP13 and MMP20, the polymorphic alleles were observed more frequently in individuals with caries experience, with a significant association only for rs478927 polymorphism in the gene encoding MMP13 (p=0.043). With respect to DED, the polymorphic alleles were observed more frequently in the genes encoding MMP8, MMP13 and MMP20, with a significant association only for the rs478927 polymorphism in the gene encoding MMP13 (p=0.005). There was a significant difference in the distribution of genotypes between the control and DED groups (p = 0.017) for the gene encoding MMP13. Based on the analyzed parameters and the obtained results, it was possible to conclude that in children from Manaus-AM, caries lesions are associated with obesity, and that there was an association between gene polymorphism (rs478927) in the gene encoding MMP13 with presence of caries lesions and DED