Abstract Genetic, epigenetic and environmental factors play an important role in the genesis of Type 2 Diabetes Mellitus (T2D). In the genetic context, one of the strategies used to investigate possible associations with diabetes is the search for Single Nucleotide Polymorphisms (SNPs), involving the comparison of alelle frequencies, the phenotypic variations and other relevant factors, such as environmental influences and lifestyle choices, Thus, the aim of this study was to find the relationship of risk variants for T2D in SNPs (rs4994) in the ADRB3 gene; (rs1799854) in the ABCC8 gene; (rs7901695 and rs12255372) in the TCF7L2 gene; and (rs8050136) in the FTO gene in a sample of the population of the municipality of Santarém (PA), Brazilian Amazon, in the northern region of Brazil. ABCC8 (rs1799854 C>T) showed a statistically significant association with T2D. Each chosen gene and SNP has been previously implicated in T2D risk according to existing scientific literature, owing to their roles in glucose regulation and body fat. Genetic TD . T D (T2D) context SNPs, , (SNPs) frequencies choices Thus rs4994 rs (rs4994 ADRB rs1799854 ABCC rs7901695 (rs790169 rs12255372 TCFL TCF L TCF7L rs8050136 (rs8050136 PA, PA (PA) Amazon Brazil (rs179985 C>T CT C literature fat (T2D (SNPs rs499 (rs499 rs179985 rs790169 (rs79016 rs1225537 rs805013 (rs805013 (PA (rs17998 rs49 (rs49 rs17998 rs79016 (rs7901 rs122553 rs80501 (rs80501 (rs1799 rs4 (rs4 rs1799 rs7901 (rs790 rs12255 rs8050 (rs8050 (rs179 (rs rs179 rs790 (rs79 rs1225 rs805 (rs805 (rs17 rs17 rs79 (rs7 rs122 rs80 (rs80 (rs1 rs1 rs7 rs12 rs8 (rs8

Abstract This study was carried out to investigate the frequency of genetic variants related to body mass index (BMI) and type 2 diabetes (T2D) and evaluating the potential impact of risk alleles on susceptibility to these disorders in six indigenous peoples from Brazilian Amazon region. The majority of Fst values for pairwise population comparisons among the indigenous groups are low or moderate. The indigenous people show high values of differentiation with Africans, Europeans and Southeast Asians and moderate values with East Asian and American populations, as expected. The allelic frequencies among indigenous indicate that the majority of associations observed with T2D in continental populations can be replicated in native Amazonians. The genetic risk scores calculated for T2D in indigenous are high and similar to those calculated for Americans and East Asians, while the estimates obtained for obesity are low, probably due to the low frequencies of the risk allele of the FTO gene found in our samples. ADRB3-rs4994 and ABCC8-rs1799854 genes showed a significant association with BMI and waist circumference, and the KCNJ11-rs5219 gene with hyperglycemia. These results emphasize the importance of knowing the genetic variability underlying complex genetic diseases in indigenous peoples and the search for particular or rare variants.

Abstract Glucose-6-phosphate dehydrogenase deficiency (G6PDd) and Duffy-negative blood group are two red blood cells variants that confer protection against malaria. In this study, the distribution of the most common G6PD variants (G6PD*A-, GGPD*A and G6PD Mediterranean) and the major alleles of the Duffy blood group (FY*A, FY*B and FY*BES) were investigated in an Afro-descendant population from state of Pará, Brazilian Amazon. G6PD variants and Duffy blood group alleles were determined by TaqMan SNP genotyping assay. Overall, molecular genotyping revealed the presence of G6PD variants in 126 (24%) of the individuals studied (5% male and 19% female), and frequencies of the G6PD*A- and G6PD*A alleles were 0.061 and 0.104, respectively. Duffy blood group genotyping showed that 24.3% of people were Duffy-negative and 41.3% were heterozygous for FY*BES. The frequency of allele FY*BES was 41.0%. The results emphasize the need to monitor G6PD deficiency for the use of primaquine in the routine care of the Afro-descendant communities of the Trombetas, Erepecuru and Cumná rivers, evaluating the risks of hemolytic crisis in case of recurrence of malaria in the region. In addition, the possible greater protection against malaria conferred by these erythrocyte polymorphisms deserves to be better investigated and explored among these Afro-descendants.

ABSTRACT Objective to profile adherence to antiretroviral therapy (ART) by patients with human immunodeficiency virus lipodystrophy syndrome (HIVLS) at a specialized unit in Pará, Brazil. Method this quali-quantitative study, involving a questionnaire and medical records of 124 patients, was conducted from February to March 2013, after research ethics approval. In the analysis, statistical tests were related by variance (p<0.05), and data were presented in table form. Results the difficulties of understanding and knowing the therapeutic regimen, mellitus diabetes and changes in lipodystrophy were significant in the interference of ART adherence. The irregular adherence group is at risk for treatment efficacy. The others have the possibility of migrating from one group to another at any time. Conclusion the profile of adherence to ART is not defined by socioeconomic data. Participation in membership groups should be encouraged as a factor in reversing the pattern of abandonment.

RESUMEN Objetivo describir el perfil de adhesión a la terapia antirretroviral (TARV) de pacientes con síndrome lipodistrófico del virus de la inmunodeficiencia humana (SLHIV), en una unidad especializada del Estado de Pará, Brasil. Método: estudio cualiquantitativo involucrando cuestionario e historias clínicas de 124 pacientes, en el período de febrero y marzo de 2013, después de la aprobación por el Comité de Ética. En el análisis, la varianza (p <0,05) articuló pruebas estadísticas, con datos presentados en tablas. Resultados las dificultades en entender y conocer el esquema terapéutico, la Diabetes Mellitus y las alteraciones de la lipodistrofia fueron significantes en la interferencia de la adhesión a la TARV. El grupo de adhesión irregular está en riesgo para la eficacia del tratamiento. Los demás tienen la posibilidad de migración de un grupo a otro en cualquier momento. Conclusión el perfil de adhesión a la TARV no está definido por datos socioeconómicos. La participación en grupos de adhesión debe ser estimulada como factor de reversión del patrón de abandono.

RESUMO Objetivo descrever o perfil de adesão à terapia antirretroviral (TARV) de pacientes com Síndrome Lipodistrófica do Vírus da Imunodeficiência Humana (SLHIV), em uma unidade especializada do Estado do Pará, Brasil. Método estudo qualiquantitativo, envolvendo questionário e prontuários de 124 pacientes, no período de fevereiro e março de 2013, após aprovação por Comitê de Ética. Na análise, a variância (p<0,05) articulou testes estatísticos, com dados apresentados em tabelas. Resultados as dificuldades de entender e conhecer o esquema terapêutico, o Diabetes Mellitus e as alterações da lipodistrofia foram significantes na interferência da adesão à TARV. O grupo de adesão irregular está em risco para a eficácia do tratamento. Os demais têm a possibilidade de migração de um grupo para outro a qualquer momento. Conclusão o perfil de adesão à TARV não é definida por dados socioeconômicos. A participação em grupos de adesão deve ser estimulada como fator de reversão do padrão de abandono.

The most common hemoglobinopathies, viz, hemoglobins S and C, and α-and β-thalassemias, were investigated through the molecular screening of 116 subjects from the community of Saracura, comprising fugitive African slaves from farms of the municipality of Santarém, in the west of Pará State, Brazilian Amazon. The observed frequency of the HBB*S gene (0.9%) was significantly lower than that encountered in other Afro-derived communities in the region. Concomitantly, the absence of the HBB*C allele has been reported for most of the Afro-Amazonian communities thus far studied. As remnant populations of quilombos are generally small, the heterogeneous distribution of HBB*S and HBB*C alleles among them is probably due to genetic drift and/or founder effect. The observed frequency of 3.7 kb deletion in Saracura (8.5%) was consistent with the African origin of the population, with a certain degree of local differentiation and admixture with individuals of Caucasian ancestry, placed in evidence by the occurrence of - -(MED) deletion (1.2%), a common mutation in Mediterranean regions. As regards f-thalassemia, among the seven different mutations found in Saracura, three βºand two β+ mutations were of Mediterranean origin, and two β+ of African. Thus, only 28% of the local β-thalassemia mutations found in Saracura were of African origin.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (P450c21, CYP21) accounts for about 95% of all CAH cases. The incidence of CYP21 gene mutations has been extensively studied in the last years, but in Brazil it has been investigated only in Southeast Brazilian patients. This study is the first report on the distribution of CYP21 mutations in patients from the Amazon region. Direct sequencing of the CYP21 gene identified at least one mutation in 96% of the studied chromosomes. The most common mutations found were IVS2-13A/C > G (36%), Q318X (12%), V281L (12%), 1760_1761insT (9%), Cluster E6 (7%), and P30L (7%). The worldwide most common mutations were identified among patients from the Amazon region at frequencies that may be expected for a population resulting from the admixture of Europeans (predominantly Portuguese), African Blacks and Amerindians, in proportions that differ from those estimated for South Brazilian populations. Interethnic mixture may explain the differences in the frequencies of some mutations between Brazilian patients from the Amazon and from the Southeast of the country. However, the differences found may also be due to variation in the number of patients with the different clinical forms of 21-hydroxylase deficiency in the studies carried out so far.

Different risk factors for venous thromboembolism (VTE) have been identified, including hereditary abnormalities in the mechanisms of coagulation and fibrinolysis. We investigated five genetic polymorphisms (FVL G1691A, FII G20210A, MTHFR C677T, TAFI A152G and TAFI T1053C) associated with VTE in individuals from the city of Belém in the Brazilian Amazon who had no history of VTE. No significant difference was found between the observed and expected genotype frequencies for the loci analyzed. We found high frequencies of MTHFR C677T (33.9%) and TAFI T1053C (74%) and low frequencies of FVL (1.6%), FII G20210A (0.8%) and TAFI A152G (0.8%). The FVL G1691A, FII G20210A and MTHFR C677T frequencies were similar to those for European populations and populations of European descent living in the city of Ribeirão Preto in the Brazilian state of São Paulo. The frequency of the two TAFI mutations in the Belém individuals was not significantly different from that described for individuals from Ribeirão Preto. We suggest that the risks for VTE in the population of Belém are of the same magnitude as that observed in European populations and in populations with an expressive European contribution.

The distribution of genetic polymorphisms of chemokine receptors CCR5-delta32, CCR2-64I and chemokine (SDF1-3’A) mutations were studied in 110 Human Immunodeficiency Virus type 1 (HIV-1) seropositive individuals (seropositive group) and 139 seronegative individuals (seronegative group) from the population of the northern Brazilian city of Belém which is the capital of the state of Pará in the Brazilian Amazon. The CCR5-delta32 mutation was found in the two groups at similar frequencies, i.e. 2.2% for the seronegative group and 2.7% for the seropositive group. The frequencies of the SDF1-3’A mutation were 21.0% for the seronegative group and 15.4% for the seropositive group, and the CCR2-64I allele was found at frequencies of 12.5% for the seronegative group and 5.4% for the seropositive group. Genotype distributions were consistent with Hardy-Weinberg expectations in both groups, suggesting that none of the three mutations has a detectable selective effect. Difference in the allelic and genotypic frequencies was statistically significant for the CCR2 locus, the frequency in the seronegative group being twice that found in the seropositive group. This finding may indicate a protective effect of the CCR2-64I mutation in relation to HIV transmission. However, considering that the CCR2-64I mutation has been more strongly associated with a decreased risk for progression for AIDS than to the resistance to the HIV infection, this could reflect an aspect of population structure or a Type I error.

The distribution of b-globin gene haplotypes was studied in 209 Amerindians from eight tribes of the Brazilian Amazon: Asurini from Xingú, Awá-Guajá, Parakanã, Urubú-Kaapór, Zoé, Kayapó (Xikrin from the Bacajá village), Katuena, and Tiriyó. Nine different haplotypes were found, two of which (n. 11 and 13) had not been previously identified in Brazilian indigenous populations. Haplotype 2 (+ - - - -) was the most common in all groups studied, with frequencies varying from 70% to 100%, followed by haplotype 6 (- + + - +), with frequencies between 7% and 18%. The frequency distribution of the b-globin gene haplotypes in the eighteen Brazilian Amerindian populations studied to date is characterized by a reduced number of haplotypes (average of 3.5) and low levels of heterozygosity and intrapopulational differentiation, with a single clearly predominant haplotype in most tribes (haplotype 2). The Parakanã, Urubú-Kaapór, Tiriyó and Xavante tribes constitute exceptions, presenting at least four haplotypes with relatively high frequencies. The closest genetic relationships were observed between the Brazilian and the Colombian Amerindians (Wayuu, Kamsa and Inga), and, to a lesser extent, with the Huichol of Mexico. North-American Amerindians are more differentiated and clearly separated from all other tribes, except the Xavante, from Brazil, and the Mapuche, from Argentina. A restricted pool of ancestral haplotypes may explain the low diversity observed among most present-day Brazilian and Colombian Amerindian groups, while interethnic admixture could be the most important factor to explain the high number of haplotypes and high levels of diversity observed in some South-American and most North-American tribes.

The allele frequency distributions of three VNTR (D1S80, APOB and D4S43) and three STR (vW1, F13A1 and DYS19) loci were investigated in two Afro-Brazilian populations from the Amazon: Curiau and Pacoval. Exact tests for population differentiation revealed significant differences in allele frequency between populations only for the D1S80 and APOB loci. A statistically significant deviation from the Hardy-Weinberg equilibrium was observed only in the D1S80 locus of the Pacoval sample. A neighbor-joining tree was constructed based on DA genetic distances of allele frequencies in four Afro-Brazilian populations from the Amazon (Pacoval, Curiau, Trombetas, and Cametá), along with those from Congo, Cameroon, Brazilian Amerindians, and Europeans. This analysis revealed the usefulness of these Amp-FLPs for population studies - African and African-derived populations were closely grouped, and clearly separated from Amerindians and Europeans. Estimates of admixture components based on the gene identity method revealed the prevalence of the African component in both populations studied, amounting to 51% in Pacoval, and to 43% in Curiau. The Amerindian component was also important in both populations (37% in Pacoval, and 24% in Curiau). The European component reached 33% in Curiau.

A região amazônica brasileira abriga diversas comunidades formadas por descendentes de escravos africanos, algumas das quais ainda relativamente isoladas. Nós estudamos duas dessas comunidades (Pacoval e Curiau), localizadas na área rural do município de Alenquer, Pará, e na região metropolitana de Macapá, Amapá, respectivamente. Entre os 12 loci investigados, alelos considerados como marcadores de ancestralidade africana, tais como HBB*S, HBB*C, TF*D1, HP*2M, ABO*B, RH*D- e CA2*2, foram encontrados com freqüências elevadas, de acordo com o esperado para populações com origem predominantemente africana. As estimativas de mistura racial indicaram que o percentual de contribuição africana em Curiau (74%) é maior do que em Pacoval (44%) e que em Curiau não foi detectada mistura com indígenas. As estimativas de ancestralidade africana estão de acordo com o grau de isolamento e com a mobilidade das comunidade estudadas. Pacoval apresenta um elevado percentual de imigrantes entre os pais e avós dos individuos estudados, enquanto que a comunidade de Curiau, apesar de situada na região metropolitana de Macapá, apresenta uma pequena proporção de imigrantes, sugerindo a existência de uma barreira relativamente forte contra a mistura interétnica. A análise dos dados genéticos foi também efetuada em sub-amostras constituídas apenas por indivíduos cujos pais e avós nasceram na localidade em estudo e que provavelmente representam essas populações duas gerações atrás. Os resultados indicaram que a mistura com não-negros nas duas populações não é um evento recente.

The Amazon region of Brazil includes communities founded by escaped slaves, some of which still remain relatively isolated. We studied two such Afro-Brazilian communities (Pacoval and Curiau), in the rural area of Alenquer, Pará, and in the metropolitan region of Macapá, Amapá, respectively. Among 12 blood loci, alleles considered as markers of African ancestry, such as HBB*S, HBB*C, TF*D1, HP*2M, ABO*B, RH*D-, and CA2*2 were found at frequencies that are expected for populations with a predominantly African origin. Estimates of interethnic admixture indicated that the degree of the African component in Curiau (74%) is higher than that of Pacoval (44%); an Amerindian contribution was not detected in Curiau. Estimated values of African ancestry fit well with the degree of isolation and mobility of the communities. Pacoval exhibited a high proportion of immigrants among the parents and grandparents of the individuals studied, whereas persons living in Curiau exhibited a low level of mobility, despite its location in the metropolitan area of Macapá city, suggesting a relatively strong barrier against the interethnic admixture in this population. In addition, analysis of genetic data in a sub-sample consisting of individuals whose parents and grandparents were born in the study site, and that probably represents the populations two generations ago, indicated that gene flow from non-black people is not a recent event in both populations.

Com o objetivo de investigar a origem da mutação <FONT FACE="Symbol">b</font>S na população da região norte do Brasil, foram analisados polimorfismos de DNA no complexo de genes <FONT FACE="Symbol">b</font> da hemoglobina em 30 pacientes com anemia falciforme na população de Belém, a capital do Estado do Pará. Sessenta e sete por cento dos cromossomos <FONT FACE="Symbol">b</font>S analisados apresentaram o haplótipo Bantu, 30% o haplótipo Benin e 3% o haplótipo Senegal. A origem da mutação<FONT FACE="Symbol"> b</font>S na população de Belém, estimada de acordo com a distribuição de haplótipos, não está de acordo com a esperada com base em dados históricos sobre o tráfico de escravos para a região norte, os quais indicam uma reduzida contribuição de escravos da região do Benin. Essas diferenças podem ser atribuídas ao tráfico interno de escravos, bem como ao posterior fluxo de populações imigrantes, particularmente de nordestinos. A distribuição de haplótipos em Belém não difere significativamente da observada em outras regiões brasileiras, muito embora os dados históricos sugiram que a maioria dos escravos procedentes da região do Atlântico-Oeste africano, onde predomina o haplótipo Senegal, foi trazida para o norte do Brasil, enquanto que o nordeste (Bahia, Pernambuco e Maranhão) recebeu o maior contingente de escravos oriundos da região centro-oeste africana, onde o haplótipo Benin é o mais comum. Nós sugerimos que as diferenças regionais quanto à procedência dos escravos africanos também foram modificadas pelo tráfico de escravos estabelecido entre as diferentes regiões brasileiras e posteriormente pelos movimentos migratórios.

We analyzed DNA polymorphisms in the <FONT FACE="Symbol">b</font>-globin gene cluster of 30 sickle cell anemia patients from Belém, the capital city of the State of Pará, in order to investigate the origin of the <FONT FACE="Symbol">b</font>S mutation. Sixty-seven percent of the <FONT FACE="Symbol">b</font>S chromosomes were Bantu type, 30% were Benin type, and 3% were Senegal type. The origin of the <FONT FACE="Symbol">b</font>S mutation in this population, estimated on the basis of <FONT FACE="Symbol">b</font>S-linked haplotypes, contradicts the historical records of direct slave trade from Africa to the northern region of Brazil. Historical records indicate a lower percentage of people from Benin. These discrepancies are probably due to domestic slave trade and later internal migrations, mainly from northeastern to northern regions. Haplotype distribution in Belém did not differ significantly from that observed in other Brazilian regions, although historical records indicate that most slaves from Atlantic West Africa, where the Senegal haplotype is prevalent, were destined for the northern region, whereas the northeast (Bahia, Pernambuco and Maranhão) was heavily supplied with slaves from Central West Africa, where the Benin haplotype predominates.