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Genetic and epidemiological aspects of implantation defects : Studies on recurrent miscarriage, preeclampsia and oocyte donationElenis, Evangelia January 2016 (has links)
Implantation requires complex molecular and cellular events involving coagulation, angiogenesis and immunological processes that need to be well regulated for a pregnancy to establish and progress normally. The overall aim of this thesis was to study different models associated with atypical angiogenesis, impaired implantation and/or placentation, such as recurrent miscarriage (RM), oocyte donation (OD) and preeclampsia. Histidine-rich glycoprotein (HRG), a serum protein with angiogenic potential has been previously shown to have an impact on implantation and fertility. In two retrospective case-control studies, women suffering from RM (Study I) and gestational hypertensive disorders (GHD) (Study IV) have been compared to healthy control women, regarding carriership of HRG genotypes (HRG A1042G and C633T SNP, respectively). According to the findings of this thesis, heterozygous carriers of the HRG A1042G SNP suffer from RM more seldom than homozygous carriers (Study I). Additionally, the presence of the HRG 633T allele was associated with increased odds of GHD (GHD IV). Studies II and III comprised a national cohort of relatively young women with optimal health status conceiving singletons with donated oocytes versus autologous oocytes (spontaneously or via IVF). We explored differences in various obstetric (Study II) and neonatal (Study III) outcomes from the Swedish Medical Birth Register. Women conceiving with donated oocytes had a higher risk of GHD, induction of labor and cesarean section, as well as postpartum hemorrhage and retained placenta, when compared to autologously conceiving women. OD infants had higher odds of prematurity and lower birthweight and length when born preterm, compared to neonates from autologous oocytes. With regard to the indication of OD treatment, higher intervention but neverthelss favourable neonatal outcomes were observed in women with diminished ovarian reserve; the risk of GHD did not differ among OD recipients after adjustment. In conclusion, HRG genetic variation appears to contribute to placental dysfunction disorders. HRG is potential biomarker that may contribute in the prediction of the individual susceptibility for RM and GHD. Regarding OD in Sweden, the recipients-despite being of optimal age and health status- need careful preconceptional counselling and closer prenatal monitoring, mainly due to increased prevalence of hypertensive disorders and prematurity.
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Ocorrência familial e associação de polimorfismos dos genes H19 e IGF2 com as Síndromes Hipertensivas Gestacionais / Familial Occurrence and H19 and IGF2 Polymorphism Association with Gestational Hypertensive DisordersAraujo, Francielle Marques 05 March 2007 (has links)
ARAUJO, F. M. Ocorrência Familial e Associação de Polimorfismos dos Genes H19 e IGF2 com as Síndromes Hipertensivas Gestacionais. 2007. 118f. Disertação (Mestrado) Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, 2007. As síndromes hipertensivas gestacionais [Pré-eclâmpsia/eclâmpsia (PE/E), hipertensão gestacional (HG) e hipertensão arterial crônica (HAC)] estão entre as maiores causas de morte materna e fetal. A PE é a mais prevalente dessas síndromes e o papel dos fatores genéticos na sua etiologia é bem aceito, embora o padrão de herança seja ainda assunto para debate. Os genes H19 e IGF2 sofrem imprinting (marcação) genômico e estão envolvidos na formação placentária e no desenvolvimento fetal. O objetivo do presente trabalho foi a pesquisa de ocorrência familial e da associação com os polimorfismos H19/RsaI e do IGF2/ApaI das síndromes hipertensivas gestacionais e do peso do recém-nascido. Todas as pacientes do estudo foram atendidas no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo e o projeto foi aprovado pelo Comitê de Ética deste hospital e pela Comissão Nacional de Ética em Pesquisa. Para a condução do estudo familial foram selecionadas 226 mulheres (75 apresentavam PE, 49 com HG e 102 do grupo controle). Os dados foram analisados pelos Testes Exato de Fisher e do Qui-quadrado, resultando em uma maior freqüência estatisticamente significativa (p <0,05) de parentes de primeiro-grau com PE/E entre o grupo de PE/E comparado aos outros grupos. Não foi observada influência da cor da pele na distribuição entre os grupos de pacientes. Para a pesquisa de polimorfismos de comprimento de fragmento de restrição H19/RsaI (alelos A e B) e IGF2/ApaI (alelos A e G) através da reação em cadeia da polimerase , foi extraído DNA de sangue periférico de 236 pacientes (55 apresentavam PE, 40 com HG, 34 com HAC e 107 do grupo controle). Os resultados, analisados através dos Testes do Qui-quadrado e G, não mostraram associação estatisticamente significativa entre os polimorfismos e as síndromes hipertensivas gestacionais ou HAC. Houve uma maior freqüência do alelo G na população estudada. Foi observado que em torno de 80% das pacientes dos quatro grupos estudados apresentou pelo menos uma cópia do alelo B e uma do alelo G, concomitantemente. A associação do peso do recém-nascido com os polimorfismos foi analisada utilizando-se os Testes Kolmogorov-Smirnov (a P<0,05) e os Não-paramétricos de Kruskal-Wallis (a P<0,05), não tendo sido evidenciadas diferenças estatisticamente significativas. No grupo da PE houve uma diminuição estatisticamente significativa do peso dos recém-nascidos quando não havia correção para a idade gestacional. Embora não tenha sido evidenciada correlação entre os polimorfismos e os fenótipos estudados, trabalhos futuros com um número amostral maior serão importantes para auxiliar no entendimento do envolvimento de fatores epigenéticos nas síndromes hipertensivas gestacionais e fornecer indícios para a prevenção, o tratamento e o aconselhamento genético. / ARAUJO, F. M. Familial Occurrence and H19 and IGF2 Polymorphism Association with Gestational Hypertensive Disorders. 2007. 118p. Dissertation (Master\'s degree) - University of Medicine, University of São Paulo, Ribeirão Preto, 2007. Gestational hypertensive disorders [preeclampsia/eclampsia (PE/E), gestational hypertension (GH) and chronic hypertension (CH)] are among the largest causes of maternal and fetal death. PE is the more prevalent of those syndromes and the role of the genetic factors in its etiology is well accepted, although the pattern of inheritance is still subject for debate. The imprinted genes H19 and IGF2 are involved in the placental formation and in the fetal development. The objective of the present study was to verify the familial occurrence of these disorders and the H19/RsaI and IGF2/ApaI polymorphism association with gestational hypertensive disorders and the weight of the newborn. All patients of the study were referred to the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, University of São Paulo, and the project was approved by the Hospital Ethic Committee and the National Commission of Ethics in Research. For the familial study, 226 women were selected (75 presented PE/E, 49 with GH and 102 from the control group). The data were analyzed by Exact of Fisher and Qui-square tests, and the frequency of families with at least one female first-degree relative (mothers and/or sisters) with PE/E was higher among the PE/E group compared to the other groups, and it was statistically significant (P<0.05). There was no statistically significant influence of the \"skin color\". Blood samples of 236 pregnant women (55 with PE/E, 40 with GH, 34 with CH and 107 from the control group) were obtained for DNA extraction, and PCR. Genotyping was carried out by enzymatic digestion with ApaI (IGF2) and RsaI (H19). The statistical analyses were performed by Qui-square and G tests. The genotypes were not significantly associated with the different groups. A higher frequency of the G allele (IGF2) was observed. Around 80% of the patients presented at least one copy of the allele B (H19) and G (IGF2), concomitantly. The association of the weight of the newborn with the polymorphisms was analyzed using the Kolmogorov-Smirnov (P <0.05) and the No-parametric Test of Kruskal-Wallis (P <0.05) tests, and statistically significant differences were not evidenced. In the group of the PE/E there was a statistically significant decrease of the weight of the newborn when the correction for the gestational age was not carried out. Although correlation has not been evidenced between the polymorphisms and the phenotypes, future studies with a higher number of patients and other imprinted genes will be important to elucidate the involvement of epigenetic factors for the prevention, treatment and genetic counseling of the gestational hypertensive disorders
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Ocorrência familial e associação de polimorfismos dos genes H19 e IGF2 com as Síndromes Hipertensivas Gestacionais / Familial Occurrence and H19 and IGF2 Polymorphism Association with Gestational Hypertensive DisordersFrancielle Marques Araujo 05 March 2007 (has links)
ARAUJO, F. M. Ocorrência Familial e Associação de Polimorfismos dos Genes H19 e IGF2 com as Síndromes Hipertensivas Gestacionais. 2007. 118f. Disertação (Mestrado) Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, 2007. As síndromes hipertensivas gestacionais [Pré-eclâmpsia/eclâmpsia (PE/E), hipertensão gestacional (HG) e hipertensão arterial crônica (HAC)] estão entre as maiores causas de morte materna e fetal. A PE é a mais prevalente dessas síndromes e o papel dos fatores genéticos na sua etiologia é bem aceito, embora o padrão de herança seja ainda assunto para debate. Os genes H19 e IGF2 sofrem imprinting (marcação) genômico e estão envolvidos na formação placentária e no desenvolvimento fetal. O objetivo do presente trabalho foi a pesquisa de ocorrência familial e da associação com os polimorfismos H19/RsaI e do IGF2/ApaI das síndromes hipertensivas gestacionais e do peso do recém-nascido. Todas as pacientes do estudo foram atendidas no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo e o projeto foi aprovado pelo Comitê de Ética deste hospital e pela Comissão Nacional de Ética em Pesquisa. Para a condução do estudo familial foram selecionadas 226 mulheres (75 apresentavam PE, 49 com HG e 102 do grupo controle). Os dados foram analisados pelos Testes Exato de Fisher e do Qui-quadrado, resultando em uma maior freqüência estatisticamente significativa (p <0,05) de parentes de primeiro-grau com PE/E entre o grupo de PE/E comparado aos outros grupos. Não foi observada influência da cor da pele na distribuição entre os grupos de pacientes. Para a pesquisa de polimorfismos de comprimento de fragmento de restrição H19/RsaI (alelos A e B) e IGF2/ApaI (alelos A e G) através da reação em cadeia da polimerase , foi extraído DNA de sangue periférico de 236 pacientes (55 apresentavam PE, 40 com HG, 34 com HAC e 107 do grupo controle). Os resultados, analisados através dos Testes do Qui-quadrado e G, não mostraram associação estatisticamente significativa entre os polimorfismos e as síndromes hipertensivas gestacionais ou HAC. Houve uma maior freqüência do alelo G na população estudada. Foi observado que em torno de 80% das pacientes dos quatro grupos estudados apresentou pelo menos uma cópia do alelo B e uma do alelo G, concomitantemente. A associação do peso do recém-nascido com os polimorfismos foi analisada utilizando-se os Testes Kolmogorov-Smirnov (a P<0,05) e os Não-paramétricos de Kruskal-Wallis (a P<0,05), não tendo sido evidenciadas diferenças estatisticamente significativas. No grupo da PE houve uma diminuição estatisticamente significativa do peso dos recém-nascidos quando não havia correção para a idade gestacional. Embora não tenha sido evidenciada correlação entre os polimorfismos e os fenótipos estudados, trabalhos futuros com um número amostral maior serão importantes para auxiliar no entendimento do envolvimento de fatores epigenéticos nas síndromes hipertensivas gestacionais e fornecer indícios para a prevenção, o tratamento e o aconselhamento genético. / ARAUJO, F. M. Familial Occurrence and H19 and IGF2 Polymorphism Association with Gestational Hypertensive Disorders. 2007. 118p. Dissertation (Master\'s degree) - University of Medicine, University of São Paulo, Ribeirão Preto, 2007. Gestational hypertensive disorders [preeclampsia/eclampsia (PE/E), gestational hypertension (GH) and chronic hypertension (CH)] are among the largest causes of maternal and fetal death. PE is the more prevalent of those syndromes and the role of the genetic factors in its etiology is well accepted, although the pattern of inheritance is still subject for debate. The imprinted genes H19 and IGF2 are involved in the placental formation and in the fetal development. The objective of the present study was to verify the familial occurrence of these disorders and the H19/RsaI and IGF2/ApaI polymorphism association with gestational hypertensive disorders and the weight of the newborn. All patients of the study were referred to the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, University of São Paulo, and the project was approved by the Hospital Ethic Committee and the National Commission of Ethics in Research. For the familial study, 226 women were selected (75 presented PE/E, 49 with GH and 102 from the control group). The data were analyzed by Exact of Fisher and Qui-square tests, and the frequency of families with at least one female first-degree relative (mothers and/or sisters) with PE/E was higher among the PE/E group compared to the other groups, and it was statistically significant (P<0.05). There was no statistically significant influence of the \"skin color\". Blood samples of 236 pregnant women (55 with PE/E, 40 with GH, 34 with CH and 107 from the control group) were obtained for DNA extraction, and PCR. Genotyping was carried out by enzymatic digestion with ApaI (IGF2) and RsaI (H19). The statistical analyses were performed by Qui-square and G tests. The genotypes were not significantly associated with the different groups. A higher frequency of the G allele (IGF2) was observed. Around 80% of the patients presented at least one copy of the allele B (H19) and G (IGF2), concomitantly. The association of the weight of the newborn with the polymorphisms was analyzed using the Kolmogorov-Smirnov (P <0.05) and the No-parametric Test of Kruskal-Wallis (P <0.05) tests, and statistically significant differences were not evidenced. In the group of the PE/E there was a statistically significant decrease of the weight of the newborn when the correction for the gestational age was not carried out. Although correlation has not been evidenced between the polymorphisms and the phenotypes, future studies with a higher number of patients and other imprinted genes will be important to elucidate the involvement of epigenetic factors for the prevention, treatment and genetic counseling of the gestational hypertensive disorders
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