O eixo hipotálamo-pituitária-adrenal é o principal sistema neuroendócrino envolvido na regulação e adaptação da resposta ao estresse e, o principal hormônio secretado é o cortisol. O cortisol exerce seus efeitos por meio dos receptores mineralocorticoide (MR) e glicocorticoide (GR). Variações nos genes desses receptores têm sido associadas à sensibilidade aos glicocorticoides e mudanças no perfil metabólico. O objetivo geral desse trabalho foi compreender a variabilidade existente em relação às respostas fisiológicas de bovinos por meio da identificação de polimorfismos genéticos em genes envolvidos na resposta ao estresse e, verificar as consequências dessa variação genética em características de qualidade da carne. Dessa forma, três abordagens foram propostas: (1) avaliar a incidência de carne DFD (dark, firm and dry) e seu impacto no perfil metabólico, endócrino e características de qualidade da carne bovina, uma vez que o estresse é um dos principais fatores que levam a essa condição desfavorável; (2) avaliar a contribuição de fatores genéticos, por meio da identificação de polimorfismos de nucleotídeo único (SNPs), no gene do MR e GR, e suas associações com as características mensuradas; (3) avaliar os efeitos desses polimorfismos sobre o perfil proteico do músculo bovino. Foram utilizados 241 bovinos da raça Nelore. Os resultados evidenciaram implicações direta do pH 24 horas post-mortem nos atributos de cor e perdas por cozimento da carne. A incidência de carnes DFD (pH>=5,8) foi de 18,7%. Os polimorfismos identificados mostraram influenciar em algumas características mensuradas. Os SNPs NR3C2_1 e NR3C2_2 no gene do MR foram associados ao conteúdo de glicogênio muscular e nível plasmático do hormônio adrenocorticotrófico (ACTH) post-mortem, e o SNP NR3C1_1 no gene do GR foi associado aos níveis plasmático de cortisol post-mortem. As análises proteômicas demonstraram que a maioria das proteínas reguladas por esses SNPs estão envolvidas na contração muscular, metabolismo e defesa celular. Portanto, é possível inferir que o pH tem impacto nas características de qualidade da carne e que polimorfismos em MR e o GR levam a mudanças na atividade do eixo HPA, no perfil metabólico do organismo e no perfil proteico do músculo, sugerindo que esses genes estão envolvidos em uma complexidade de funções e podendo ser alvos de estudos em sistemas de produção que visam melhorar a produtividade. / The hypothalamic-pituitary-adrenal axis is the main neuroendocrine system involved in the regulation and adaptation in stress response and the primary hormone secreted is cortisol. Cortisol exerts its effects through the mineralocorticoid (MR) and glucocorticoid (GR) receptors. Variations in the genes of these receptors have been associated with sensitivity to glucocorticoids and changes in the metabolic profile. The general objective of this work was to understand the variability in relation to physiological responses of cattle through identification of genetic polymorphisms in genes involved in stress response and, checking the consequences of this genetic variation in meat quality traits. Thus, three approaches have been proposed: (1) evaluate the incidence of DFD meat (dark, firm and dry) and its impact on metabolics, endocrines profiles and meat quality traits, since stress is the major factor that lead to this unfavorable condition; (2) evaluate the contribution of genetic factors through identification single nucleotide polymorphisms (SNPs) in the MR and GR gene and its association with the measured traits; (3) evaluate the effects of these polymorphisms on the protein profile of bovine muscle. A total of 241 Nellore cattle were used. The results evidenced direct implications of 24 hours pH post-mortem in color attributes and cooking losses. The incidence of DFD meat (pH >= 5.8) was 18.7%. The polymorphisms identified demonstrated to influence some on measured characteristics. The NR3C2_1 and NR3C2_2 SNPs in MR gene were associated with muscle glycogen content and post-mortem adrenocorticotropic hormone (ACTH) plasma levels and, the NR3C1_1 SNP in GR was associated with post-mortem cortisol plasma levels. The proteomic analysis demonstrated that most proteins regulated by these SNPs are involved in muscle contraction, metabolism and cellular defense. Therefore, it is possible to infer that pH has impact on meat quality traits and MR and GR polymorphisms lead to changes in the HPA axis activity, metabolic profile and protein muscle profile, suggesting that these genes are involved in a complexity of functions and may be targets for studies on production systems to improve productivity.

Há décadas a exposição ao mercúrio é alvo de estudos toxicológicos devido ao alto potencial de danos a saúde humana. Na região amazônica os primeiros estudos reportavam a exposição ocupacional pelo uso nos garimpos de ouro, entretanto recentemente destacam-se os estudos relacionados a exposição ambiental que ocorre na região decorrente do consumo de peixes contaminados com mercúrio. Muitos estudos se concentram em populações ribeirinhas residentes na região do rio Tapajós, onde o consumo de peixes é frequente e o metil-mercúrio (MeHg) contido nos peixes é o responsável pela exposição dessas pessoas ao metal. O MeHg apresenta efeitos tóxicos relevantes sobre o sistema cardiovascular, e muitos grupos de pesquisa buscam elucidar os mecanismos que expliquem tais efeitos. Alguns estudos apontam uma diminuição significativa na disponibilidade do óxido nítrico (NO) após exposição ao organometal, o que poderia contribuir para uma alteração da fisiologia cardiovascular uma vez que o NO é um modulados desse sistema. O NO é sintetizado pela óxido nítrico sintase endotelial (eNOS) e sua atividade pode ser alterada por vários fatores, dentre eles, os polimorfismos nos genes que codificam essa proteína, são eles: T-786C na região promotora, 27-pb VNTR no intron 4 e Glu298Asp no exon 7. Neste sentido, o presente estudo teve por objetivo avaliar os efeitos dos polimorfismos da eNOS sobre a síntese de NO entre os indivíduos expostos a metilmercúrio. Foram analisadas amostras de sangue de 214 voluntários com idade entre 15 e 84 anos, dos quais 103 homens e 111 mulheres. A concentração de mercúrio no sangue (Hg sangue) total variou de 1,7 a 179,3 µg/L e a concentração plasmática de nitrito variou entre 85,7 e 695,8 M. Foram determinados os valores de pressão arterial sistólica (PAS), pressão arterial diastólica (PAD), índice de massa corporal (IMC) e freqüência cardíaca (FC) de todos os voluntários. A PAS média foi de 119,8 mmHg e a média da PAD foi 71,8 mmHg. O IMC médio foi de 24,5 Kg/m2 e a FC média foi 70,4 batimentos por minuto (bpm). Não foram observadas diferenças entre os grupos, segundo genótipos dos três polimorfismos, quanto às características dos voluntários: idade, PAS, PAD, IMC, FC, Hg sangue e as concentrações plasmáticas de nitrito. Quando os polimorfismos foram estudados isoladamente foi observado que o alelo C na região promotora, o alelo 4b no intron 4 e o alelo Glu no exon 7 apresentaram-se associados a concentrações reduzidas e nitrito plasmático. Quando a população foi estratificada com base na concentração de Hg essa associação desapareceu, provavelmente mascarada pelas altas concentrações do metal. Entretanto quando foram estudados os haplótipos pode ser observada novamente a associação desses mesmos alelos com a diminuição da concentração do nitrito, confirmando os achados iniciais. O haplótipo mais frequente na população combina os alelos selvagens para todos os polimorfismos (T, 4b e G) e o haplótipo menos freqüente combina os alelos variantes. O haplótipo associado à menor concentração plasmática de nitrito combina os alelos selvagens (C, 4b e G), confirmando os primeiros resultados. Essa abordagem haplotípica é muito útil na observação de efeitos mais discretos uma vez que é possível observar os efeitos dos três polimorfismos agindo simultaneamente sobre uma variável, nesse caso o óxido nítrico. O presente estudo sugere que os fatores genéticos exercem grande influência sobre a produção e biodisponibilidade de NO e que esses fatores combinados com a exposição ambiental ao Hg podem agir de maneira sinérgica, aumentando a suscetibilidade aos efeitos cardiotóxicos do metal através da modulação da atividade da eNOS. / The mercury (Hg) exposure has been target of toxicological studies due the high potential of damage to human health. In the Amazon region the first studies reported the occupational exposure due the use in gold mining, however, recently become relevant the studies about the environment exposure due the fish intake in the riparian population. Several studies have been concentrated in the riparian community in the Tapajós river region, where the fish consumption is frequent and the methylmercury content in fish is responsible to exposure of this people. The MeHg presents toxic effects in the cardiovascular system and many researches groups try to elucidate the mechanisms that explain this effects. Some studies report a significant reducing in nitric oxide (NO) production after the Hg exposure, which could contribute to an altered physiology of the cardiovascular system, once the NO is a modulating factor of this system. The NO is produced by the endothelial nitric oxide synthase (eNOS) and its activity can be altered by many factors like polymorphisms in gene that codify this protein, among this: : T-786C in the promoter region, 27-pb VNTR in intron 4 and Glu298Asp in exon 7. In this regard, the present study mean to evaluate the effects of the eNOS polymorphisms over the NO synthesis among the Hg exposed subjects. In this work, the whole blood samples of 214 volunteers were analyzed for determination of Hg concentration, nitrite plasma concentration and genotyping. The age of the volunteers varied between 15 and 84 years old, including 103 men and 111 women. The blood mercury concentration varied between 1.7 and 179.3 µg/L and the nitrite plasma concentration varied between 85.7 and 695.8 M. Was determinate the systolic arterial pressure (SAP), diastolic arterial pressure (DAP), body mass index (BMI) and heart rate (HR). The SAP mean was 119.8 mmHg and the DAP mean was 71.8 mmHg. The BMI mean was 24.5 Kg/m2 and the HR mean was 70.4 beats per minute. There was no difference among the groups of the three polymorphisms according the volunteers characteristics: age, DAP, SAP, BMI, HR, blood Hg concentration and nitrite plasma concentration. When the polymorphisms were observed separately the reduced nitrite plasma concentration was associated with the presence of the alleles: C in promoter region, 4b in intron 4 and G in exon 7, however there is lack of association when the volunteers were grouped according the blood Hg concentration, probably due a mask effect of the high Hg concentration. When these three polymorphisms were observed simultaneously, in analysis of the haplotypes, the association between the same alleles and the nitrite plasma concentration was observed again, confirming the initial findings. The commonest haplotype in the volunteers combine the alleles of the three polymorphisms (T, 4b and G) and the less frequent haplotype combine the three variants alleles. There was an association between the haplotype C, 4b and G and reduced nitrite plasma concentration, according the result of the polymorphisms separately. The haplotype analysis is too interesting to observe discrete effects, once is possible to analyze the effects of the three polymorphisms acting simultaneously above one variable, in this case, nitric oxide production. The present study suggest that genetic factors could exert a relevant influence above the NO production and bioavailability and that this factors combined with environmental Hg exposure can acting synergic, increasing the susceptibility to Hg cardiovascular effects, through the modulation of the eNOS activity.

A dependência de álcool acomete de 10 a 12% da população mundial, estando a associação entre uso abusivo do álcool e pancreatite crônica bem estabelecida. A suscetibilidade pancreática ao álcool é variável e apenas 5 a 10% dos etilistas crônicos desenvolvem pancreatite crônica, sendo o papel dos fatores genéticos neste processo praticamente desconhecido. O gene CFTR (cystic fibrosis transmenbrane conductance regulator) codifica proteína que funciona na membrana plasmática de células epiteliais e que tem papel chave na função pancreática exócrina normal, promovendo a regulação, da secreção de fluídos e bicarbonato, importantes para a diluição e a alcalinização do suco pancreático. Quando a função desta proteína é inadequada, observa-se obstrução de pequenos ductos por rolhas protéicas. Várias pesquisas buscam documentar a associação fibrose cística - pancreatite crônica, porém os resultados são conflitantes. Este trabalho pesquisou a freqüência de polimorfismos no trato de politiminas e poli TGs no intron 8 do gene CFTR em pacientes portadores de pancreatite crônica alcoólica. Foram estudados três grupos de pacientes: Grupo A - adultos alcoolistas com diagnóstico de pancreatite crônica; Grupo B - adultos alcoolistas sem pancreatopatia ou cirrose hepática e Grupo C - adultos sadios não alcoolistas. O DNA genômico para análise do gene CFTR foi extraído do sangue periférico, pesquisando-se a freqüência de polimorfismos no trato de politiminas e poli TGs no intron 8. O genótipo 5T/7T foi mais encontrado no grupo A do que no B (p = 0,0481), não havendo diferença quando comparados os grupos A e C (p = 0,1317). Pacientes com pancreatite crônica por álcool com o genótipo 5T/7T tiveram menor incidência de diabetes melito do que aqueles com outros genótipos (p = 0,0465). A combinação de haplótipos 10TG 7T / 11TG 7T foi mais freqüente nos grupos B e C do que no A e poderia, eventualmente, ser um fator protetor contra o desenvolvimento da pancreatite crônica. (p = 0,0080 e 0,0162). Em conclusão, há diferenças no intron 8 do gene CFTR em pacientes com pancreatite crônica alcoólica, quando comparados com alcoolistas não pancreatopatas e indivíduos com o genótipo 5T/7T teriam maior risco de desenvolver pancreatite crônica quando se tornam alcoolistas crônicos. / The alcohol dependence affects from 10 to 12% of the world-wide population, being the association between alcohol abuse and chronic pancreatitis well established. The pancreatic susceptibility to the alcohol is only 5 to 10%, being the paper of the genetic factors practically unknown. The CFTR gene (cystic fibrosis transmenbrane conductance regulator) codifies a protein that functions in the epithelial cells and has a role in pancreatic exocrine function, promoting regulation of the secretion of fluids and bicarbonate, important for the dilution and the alcalinization of the pancreatic juice. When the function of this protein is inadequate, blockage of small ducts occurs. Some research regist the association cystic fibrosis - chronic pancreatite, however the results are conflicting. This work searched the frequency of polymorphisms in the polyT and poly TGs tracts in intron 8 of CFTR gene in patients with alcoholic chronic pancreatitis. Three groups of patients have been studied: Group A - adult alcoholics with chronic pancreatitis; Group B - adult alcoholics without pancreatic disease or hepatic cirrhosis and Group C - non alcoholics healthy adults. DNA analysis of CFTR gene was made after extraction from peripheral blood samples. The 5T/7T genotype was more frequently found in group A that in B (p = 0.0481), with no difference when compared to group C (p = 0,1317). Patients with alcoholic chronic pancreatitis and 5T/7T genotype had less incidence of diabetes mellitus that those with other genotypes (p = 0,0465). The haplotype combination 10TG 7T / 11TG 7T was more frequent in groups B and C that in A and it could, eventually, be a protective factor against the development of alcoholic chronic pancreatitis. (p = 0,0080 and 0,0162). In conclusion, we found differences when these tree groups are compared and individuals with 5T/7T genotype would have greater risk to develop chronic pancreatitis if they become alcoholics.

Deux approches ont été mises au point et utilisées afin de mieux comprendre les facteurs nutritionnels, physiopathologiques et génétiques intervenant dans la grande variabilité d'absorption du cholestérol chez l'homme (30-80%) :- le dosage de marqueurs plasmatiques d'absorption et de synthèse du cholestérol (METHODE INDIRECTE), qui s'applique aux grandes cohortes.- le dosage simultané de deux isotopes stables du cholestérol utilisés comme traceurs (METHODE DIRECTE), qui est la méthode de référence pour déterminer le taux d'absorption du cholestérol alimentaire.Nous avons déterminé, par la méthode indirecte, des interactions gène-régime-sexe, dans une population mixte présentant un risque cardiovasculaire modéré.On a montré qu'en modifiant les habitudes alimentaires, le statut d'absorption du cholestérol d'un sujet n'était pas modifié après 3 mois de régime méditerranéen, quel que soit le sexe. De plus la diminution du cholestérol circulant (LDL-C) induite par le régime de type méditerranéen était plus marquées chez les faibles absorbeurs de cholestérol. Le statut d'absorbeur est donc stable dans le temps et sous différents régimes, mais il module la réponse au régime, illustrant l'importance de ce statut dans la prise en charge nutritionnelle personnalisée des sujets. Nous avons aussi établi une interaction gène-régime sur le polymorphisme génétique du gène de la microsomal triglyceride transfer protein (-493G/T). Ce polymorphisme module le niveau d'absorption du cholestérol chez les femmes sous un régime occidental et cet effet est aboli sous un régime méditerranéen.La méthode indirecte présente cependant des limites. Aussi avons-nous mis au point une méthode de dosage directe originale, basée sur l'abondance relative des isotopomères du cholestérol, le but étant de mesurer simultanément les marqueurs directs et indirects et de comparer les deux méthodes en vue de l'application systématique de la méthode indirecte dans différentes études chez l'homme. / Two approaches were used to better understand nutritional, physio-pathological and genetic factors intervening in the great inter-individual variability of cholesterol absorption in humans (30-80%) : - INDIRECT METHOD consisting in the determination of both absorption and synthesis plasmatic markers of cholesterol, which is used in large scale studies; - a DIRECT METHOD by measuring simultaneaously two cholesterol stable isotopes, used as tracers. It is the "gold" method to determine the absorption percentage of dietary cholesterol. By using indirect method, we have shown gene-diet interactions according to sex in a population of men and women with moderate cardiovascular risks. Changing in dietary habits didn't alter cholesterol absorption statuts after 3 months of mediterranean type diet, whatever the sex. Moreover, the lowering of plasma LDL-cholesterol induced by mediterranean type diet was more marked in low-cholesterol absorbers. Thus, the cholesterol absorption status is stable over time and under differents regimes, but it modulates responsiveness to a dietary challenge. These findings illustrate the importance of cholesterol absorption status in personalized nutrition recommendations. Another finding is a gene-diet interaction in the -493G/T gene polymorphism of the microsomal triglyceride transfer protein. This polymorphism modulates the level of cholesterol absorption in women under a western diet, an effect abolished under a prudent mediterranean type diet. As indirect method shows limits, we established an original direct method, based on relative abundance of cholesterol isotopomers. Our goal is to measure simultaneously both direct and indirect plasmatic markers. Then, we could compare the two methods with the objective of applying systematically indirect method in different studies in humans.

Heart transplantation is performed in patients with end-stage heart failure, in whom all other methods of treatment failed. The most common causes of end-stage heart failure are dilated cardiomyopathy and coronary artery disease. The destiny of these patients is highly variable. Prediction of long term survival in patients after heart transplantation is not satisfactory and up to now has not been found reliable marker. Most of the patients die after heart transplantation due to cardiovascular disease. This thesis is focused on molecular genetics and statistical analysis of four single nucleotide polymorphisms, namely rs17817449 (16q12.2, FTO gene), rs2943634 (2q36.3; intergenic region), rs6922269 (6q25.1; MTHFD1L gene), and rs10757274 (9p21.3; intergenic region). According to genome wide association studies are these SNPs assosiated with cardiovascular diseases. We genotyped DNA samples of 364 heart donors and 364 heart recipients. The results were statistically compared (using OR and Pearson's χ2 test) with the control group, which consisted of samples of individuals from the general population MONICA study. We examined the genotype in patients whose hearts failed due to dilated cardiomyopathy or coronary artery disease and then in patients with cardiac allograft vasculopathy. Furthermore, we focused on...

O colágeno XVIII é um componente das membranas basais com diversos domínios funcionais, como a endostatina e o domínio frizzled, que têm importante papel em processos celulares como proliferação e diferenciação. COL18A1 possui dois promotores alternativos: o promotor 1, que regula a síntese da variante NC11-303, e o promotor 2 responsável pelas variantes NC11- 728 e NC11-493, expressas por hepatócitos. Existe uma variação interindividual da endostatina circulante e da expressão do colágeno XVIII no fígado. A expressão do colágeno XVIII/endostatina foi correlacionada com a progressão tanto do hepatocarcinoma (HCC), quanto da fibrose/cirrose hepática. Elucidar a regulação da expressão de COL18A1 pode auxiliar na compreensão dessa variação interindividual e da progressão dessas doenças. Neste trabalho demos início a caracterização do promotor 2 do COL18A1. Identificamos na seqüência predita como promotora cinco regiões conservadas entre humanos e camundongos. A análise in silico e funcional dessas regiões revelou que os fatores de transcrição, Sp1, Sp3, YY1, Oct-1, C/EBPα e C/EBPβ, interagem com as mesmas. Demonstramos que C/EBPβaumenta a taxa de transcrição do promotor 2 em hepatócitos, e que existe uma correlação positiva da expressão de NC11-493 com C/EBPαe C/EBPβem tecido hepático cirrótico e tumoral. As expressões de C/EBPαem tecido hepático cirrótico e tumoral estão diretamente correlacionadas, enquanto que os níveis de NC11-493 nos tumores estão inversamente correlacionados com o tamanho dos mesmos. Mostramos a existência de diversos SNPs no promotor 2. O SNP-700T/G, funcional in vitro, afeta a interação de Sp3 e YY1 com essa região regulatória. A deleção da região do SNP indicou que ela possui elementos importantes para a transcrição em hepatócitos, apesar deste SNP não estar relacionado com o nível de expressão do colágeno XVIII em fígado fibrótico ou com susceptibilidade a HCC. O SNP- 700T/G está em desequilíbrio de ligação com o SNPc.1135C/T, no domínio frizzled do colágeno XVIII. Não foi possível elucidar a funcionalidade do SNPs c.1135C/T in vitro, mas os haplótipos formados por esses dois SNPs têm diferentes frequências entre descendentes de europeus e de africanos. Nosso trabalho traz importantes contribuições e abre novas perspectivas para a compreensão da regulação do colágeno XVIII em fígado humano, tanto em situações fisiológicas, quanto em processos fibrogênicos e tumorigênicos¶ / Collagen XVIII is a basal membrane component with several funcional domains, such as endostatin and frizzled domains, which have important roles in cellular processes such as proliferation and differentiation. COL18A1 has two promoter regions: promoter 1, that regulates the synthesis of NC11-303 isoform, and promoter 2, localized in intron 2, responsible for NC11-728 and NC11-493 isoforms expressed by hepatocytes. There is a large interindividual variation in circulating endostatin and in collagen XVIII liver expression. Collagen XVIII/endostatin levels were correlated with hepatocellular carcinoma (HCC) progression, as well as liver fibrosis/cirrhosis, conditions that precede HCC. Elucidating the mechanisms that regulate COL18A1 expression in hepatocytes may help understanding its variation among individuals and liver disease stages, as well as contribute to new treatment strategies. In this work we began to characterize COL18A1 promoter region 2. We identified in the predicted promoter sequence five conserved regions between human and mouse. The in silico and functional analysis of these regions revealed that transcription factors Sp1, Sp3, YY1, Oct-1, C/EBPα and C/EBPβ interact with them. We have demonstrated that C/EBPβ increases promoter 2 transcription rate in hepatocytes, and that there is a positive correlation of NC11-493 expression with that of C/EBPα and C/EBPβ in cirrhotic and tumor liver samples. Non-tumor and tumor C/EBPα expressions positively correlate between themselves, while NC11-493 tumor expression inversely correlates with tumor size. We also showed that there are several SNPs in COL18A1 promoter 2 region. SNP-700T/G, functional in vitro, affects Sp3 and YY1 interaction with the promoter 2 region and deletion of the SNP region indicated that this sequence has important hepatocyte regulatory elements. Our results suggest that this SNP does not significantly affects COL18A1 expression in fibrotic/cirrhotic liver and is not associated with HCC susceptibility. SNP-700T/G is in linkage disequilibrium with SNPc.1135C/T, at collagen XVIII frizzled domain. We could not elucidate SNPc.1135C/T functionality in vitro, but the haplotypes formed by these two SNPs have different frequencies in European and African descendants. In conclusion, our work brings important contributions and opens new perspectives for the comprehension of collagen XVIII regulation in human liver in physiological situations, as well as in fibrotic/cirrhotic and tumorigenic process.

>Magister Scientiae - MSc / The burden of non-communicable diseases (NCDs) in South Africa is predicted to increase substantially in the next decades if the necessary preventative measures are not taken. The two most common NCDs associated with rapid mortality increase are diabetes mellitus (DM) and hypertension (HTN). Both of these diseases, i.e DM and HTN, can be a result of a combination of modifiable risk factors (behavioral) and non-modifiable risk factors (genetic, physiological, and environmental). New strategies implemented to manage these diseases should include addressing both modifiable and non-modifiable risk factors for patients with NCDs. The aim of this study was to contribute to the reduction of incidence of uncontrolled T2DM among patients taking metformin as a first-line anti-diabetic drug, through the development of individualized therapy for this drug. When implemented, this could be one of the healthcare strategies to address non-modifiable risk factors for patients with T2DM as an important NCD. The first objective of the study was to explore the prevalence and risk factors of DM and HTN in South Africa, especially within the economically disadvantaged population.

MSc (Microbiology) / Department of Microbiology / See the attached abstract below

MSc (Microbiology) / Department of Microbiology

Introduction: Available data suggest an association between presence of secondary (AA) amyloidosis and MCP-1 (monocyte chemoatracttant protein-1) and MIP-1alpha (macrophage inflammatory protein-1 alpha) genes polymorphisms. Some studies have also shown an impact of polymorphisms in exon 3 of SAA 1 (serum amyloid A 1) gene on the incidence of AA amyloidosis in different populations. Methods: The incidence of single genotypes MCP-1, MIP-1alpha and SAA 1 genes was investigated. Serum levels of SAA, MCP-1 and MIP-1alpha were measured and potential relation between serum levels and genotypes were analyzed. All examinations were performed in patients with AA amyloidosis (43), rheumatoid arthritis (RA) without amyloidosis and healthy control group (100). Results: Significantly more frequent occurrence of 1.1/1.1 genotype in SAA 1 was recorded in AA amyloidosis group compared to RA group as well as in control group (p<0,001). No statistically significant differences in distribution of another genotypes were found. Distribution of neither 1.1/1.1 genotype nor another ones did not vary among RA group and control group. No significant difference in distribution of another examined genotypes was recorded among all three groups. Serum concentrations of SAA were statistically significantly higher in AA amyloidosis group...