Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population.

Radiotherapy is focused on the tumor but also reaches healthy tissues, causing toxicities that are possibly related to genomic factors. In this context, radiogenomics can help reduce the toxicity, increase the effectiveness of radiotherapy, and personalize treatment. It is important to consider the genomic profiles of populations not yet studied in radiogenomics, such as the indigenous Amazonian population. Thus, our objective was to analyze important genes for radiogenomics, such as ATM, TGFB1, RAD51, AREG, XRCC4, CDK1, MEG3, PRKCE, TANC1, and KDR, in indigenous people and draw a radiogenomic profile of this population. The NextSeq 500® platform was used for sequencing reactions; for differences in the allelic frequency between populations, Fisher's Exact Test was used. We identified 39 variants, 2 of which were high impact: 1 in KDR (rs41452948) and another in XRCC4 (rs1805377). We found four modifying variants not yet described in the literature in PRKCE. We did not find any variants in TANC1-an important gene for personalized medicine in radiotherapy-that were associated with toxicities in previous cohorts, configuring a protective factor for indigenous people. We identified four SNVs (rs664143, rs1801516, rs1870377, rs1800470) that were associated with toxicity in previous studies. Knowing the radiogenomic profile of indigenous people can help personalize their radiotherapy.

Molecular Profile of Variants in CDH1, TP53, PSCA, PRKAA1, and TTN Genes Related to Gastric Cancer Susceptibility in Amazonian Indigenous Populations.

Gastric Cancer is a disease associated with environmental and genetic changes, becoming one of the most prevalent cancers around the world and with a high incidence in Brazil. However, despite being a highly studied neoplastic type, few efforts are aimed at populations with a unique background and genetic profile, such as the indigenous peoples of the Brazilian Amazon. Our study characterized the molecular profile of five genes associated with the risk of developing gastric cancer by sequencing the complete exome of 64 indigenous individuals belonging to 12 different indigenous populations in the Amazon. The analysis of the five genes found a total of 207 variants, of which 15 are new in our indigenous population, and among these are two with predicted high impact, present in the TTN and CDH1 genes. In addition, at least 20 variants showed a significant difference in the indigenous population in comparison with other world populations, and three are already associatively related to some type of cancer. Our study reaffirms the unique genetic profile of the indigenous population of the Brazilian Amazon and allows us to contribute to the conception of early diagnosis of complex diseases such as cancer, improving the quality of life of individuals potentially suffering from the disease.

Mucin (MUC) Family Influence on Acute Lymphoblastic Leukemia in Cancer and Non-Cancer Native American Populations from the Brazilian Amazon.

The mucin (MUC) family includes several genes aberrantly expressed in multiple carcinomas and mediates diverse pathways essentials for oncogenesis, in both solid and hematological malignancies. Acute Lymphoblastic Leukemia (ALL) can have its course influenced by genetic variants, and it seems more frequent in the Amerindian population, which has been understudied. Therefore, the present work aimed to investigate the MUC family exome in Amerindian individuals from the Brazilian Amazon, in a sample containing healthy Native Americans (NAMs) and indigenous subjects with ALL, comparing the frequency of polymorphisms between these two groups. The population was composed of 64 Amerindians from the Brazilian Amazon, from 12 different isolated tribes, five of whom were diagnosed with ALL. We analyzed 16 genes from the MUC family and found a total of 1858 variants. We compared the frequency of each variant in the ALL vs. NAM group, which led to 77 variants with a significant difference and, among these, we excluded those with a low impact, resulting in 63 variants, which were distributed in nine genes, concentrated especially in MUC 19 (n = 30) and MUC 3A (n = 18). Finally, 11 new variants were found in the NAM population. This is the first work with a sample of native Americans with cancer, a population which is susceptible to ALL, but remains understudied. The MUC family seems to have an influence on the development of ALL in the Amerindian population and especially MUC19 and MUC3A are shown as possible hotspots. In addition, the 11 new variants found point to the need to have their clinical impact analyzed.

Prevalence and Risk Factors for HTLV-1/2 Infection inRiverside and Rural Populations of the State of Pará.

Human T-lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) infection has been described in several Amazonian populations; however, there is still a lack of data on the prevalence of the virus in riparian populations living in rural areas of the state of Pará. The present study aimed to evaluate the prevalence of HTLV-1/2 infection in four riverine communities and one rural area in the state of Pará and to describe the possible risk factors for infection. A total of 907 individuals responded to an epidemiological survey and gave blood samples collected for anti-HTLV-1/2 antibodies by immunoenzymatic assay (EIA). The serum-reactive samples were subjected to confirmation by an in-line assay (Inno-Lia) and by proviral DNA screening using real-time PCR (qPCR). The total prevalence was 0.8% (7/907) for HTLV-1/2 (CI: 0.2-1.3%), with 0.66% HTLV-1 and 0.11% HTLV-2. The prevalence by sex was 0.7% in women (4/565) and 0.9% in men (3/342). Among seropositive patients, 83.3% (5/7) reported being sexually active, and 57.1% (4/7) reported not having the habit of using condoms during their sexual relations. Intrafamily infection was also observed. The results reinforce the need for public policies to prevent and block the spread of HTLV, especially in riparian communities that are subject to difficulties in accessing the Unified Health System (Sistema Único de Saúde/SUS) because infected individuals need clinical monitoring for surveillance and early diagnosis of symptoms associated with HTLV-1.

High prevalence of sexual infection by human papillomavirus and Chlamydia trachomatis in sexually-active women from a large city in the Amazon region of Brazil.

BACKGROUND: The Human Papillomavirus (HPV) and Chlamydia trachomatis are the most prevalent Sexually Transmitted Infections (STIs) worldwide, and are associated cervical cancer and pelvic inflammatory disease, respectively. However, 80% of women testing positive are asymptomatic. In the Amazon region, young women, in particular, are widely exposed to the infections and their consequences. OBJECTIVES: Determine the prevalence of sexual infection by HPV and C. trachomatis in young, sexually-active women treated at a university health program in a large city of the Brazilian Amazon region. METHODS: We amplified the L1 gene of HPV. We amplified ompA gene of C. trachomatis by nested PCR, and the study participants filled in a questionnaire on their social, epidemiological, and reproductive health characteristics. The data were analyzed using the Odds Ratio, to evaluate the degree of association of these variables with the observed infections. RESULTS: The prevalence of infection by HPV was 15.5% (47/303). This infection was recorded in 32.2% of the women of less than 25 years of age (OR:3.02 [CI95%] = 1.32-6.92; p = 0.014), 17.9% of the single women (OR: 2.41 [CI95%] = 1.22-4.75; p = 0.014), 23.8% of the women that reported having first sexual intercourse at less than 15 years of age (OR: 2.22 [CI95%] = 1.16-4.23; p = 0.021), 20% of those that reported having had more than one sexual partner during their lifetime (OR: 3.83 [CI95%] = 1.56-9.37; p = 0.003), and in 28.3% that use oral contraceptives (CI95% = 1.33-5.43; p = 0.008). The prevalence of sexual infection by C. trachomatis was 4.6% (14/303), and this bacterium was present in 16.1% of the young women of less than 25 years of age (OR: 2.86 [CI95%] = 1.33-5.43; p = 0.008). CONCLUSIONS: We found a high prevalence of HPV in young, unmarried women who started their sex lives early, who had several sexual partners in their lives and who used oral contraceptives. The prevalence of C. trachomatis was high only in young women. Our data are in accordance with other studies in Brazil and in the world and may serve to base the formulation of diagnostic and screening measures for these infections in women in the Amazon.

Prevalence and Risk Factors for HTLV-1/2 Infection in Quilombo Remnant Communities Living in the Brazilian Amazon.

Human T-lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) are retroviruses that originated on the African continent and dispersed throughout other continents through human migratory flows. This study describes the prevalence of HTLV-1 and HTLV-2 infection in residents of 11 quilombo remnant communities in the state of Pará, Brazil, and the associated risk factors. A total of 859 individuals (334 men and 525 women), aged between 7 and 91 years, participated in the study. All subjects answered a questionnaire with questions on sociodemographic characteristics and on risk factors associated with HTLV infection, and blood samples were collected and separated into plasma and leukocytes. An immunoenzymatic assay (ELISA; Murex HTLV-I+II, DiaSorin, Dartford, UK) was used as a screening test, and positive samples were subjected to line immunoassay confirmatory tests (Inno-LIA HTLV I/II Score FUJIREBIO) and DNA extraction for subsequent real-time PCR to differentiate the viral type. Four of the 859 individuals were seropositive for HTLV. HTLV-1 infection was confirmed in one individual from the Itamoari community (0.92%), and HTLV-2 infection was confirmed in two individuals from São Benedito (3.17%) and in one individual from Arimandeua (2.22%). Blood transfusion was the only risk factor associated with HTLV infection in this study. This study reports the occurrence of HTLV-1 and HTLV-2 in quilombo remnant communities in the state of Pará. Considering the African origin of the virus and its introduction into Brazil from the slave trade, the continued evaluation of quilombola communities in the state of Pará is essential to better characterize the distribution of infections in these populations and to create public health policies for the control of the spread of the virus and associated diseases.

HTLV-1/2 in Indigenous Peoples of the Brazilian Amazon: Seroprevalence, Molecular Characterization and Sociobehavioral Factors Related to Risk of Infection.

HTLV-1/2 infection is endemic in Indigenous peoples of the Americas. Its origin is attributed to the migratory flow of Amerindian ancestral peoples. The present study aimed to investigate the seroprevalence of HTLV-1/2 infection in Indigenous peoples of the Brazilian Amazon. A total of 3350 Indigenous people belonging to 15 communities were investigated. The investigation was performed using serological (ELISA), molecular (qPCR) and confirmatory (Western blot and/or Inno-Lia) tests to detect and differentiate the infection. The seroprevalence was 8.3% for HTLV-1/2 infection, with 0.1% of individuals seropositive for HTLV-1 and 8.1% for HTLV-2. The prevalence of infection was statistically higher in women (10.1%) than in men (6.5%) (p = 0.0002). This female predominance was observed in all age groups; in females the prevalence was significant from 41 years old (p < 0.0001) and in males from 51 years old (p < 0.0001). Here, we present a prevalence of HTLV-1/2 among Indigenous peoples of the Brazilian Amazon. The endemic infection in these groups must reflect the different epidemiological profiles observed in these peoples, such as sexual transmission through rejection of condom use, breastfeeding, especially in cases of cross-breastfeeding, and the high rate of pregnancy in the villages.

Identification of Variants (rs11571707, rs144848, and rs11571769) in the BRCA2 Gene Associated with Hereditary Breast Cancer in Indigenous Populations of the Brazilian Amazon.

Estimates show that 5-10% of breast cancer cases are hereditary, caused by genetic variants in autosomal dominant genes; of these, 16% are due to germline mutations in the BRCA1 and BRCA2 genes. The comprehension of the mutation profile of these genes in the Brazilian population, particularly in Amazonian Amerindian groups, is scarce. We investigated fifteen polymorphisms in the BRCA1 and BRCA2 genes in Amazonian Amerindians and compared the results with the findings of global populations publicly available in the 1000 Genomes Project database. Our study shows that three variants (rs11571769, rs144848, and rs11571707) of the BRCA2 gene, commonly associated with hereditary breast cancer, had a significantly higher allele frequency in the Amazonian Amerindian individuals in comparison with the African, American, European, and Asian groups analyzed. These data outline the singular genetic profiles of the indigenous population from the Brazilian Amazon region. The knowledge about BRCA1 and BRCA2 variants is critical to establish public policies for hereditary breast cancer screening in Amerindian groups and populations admixed with them, such as the Brazilian population.

HTLV in South America: Origins of a silent ancient human infection.

The description of the first human retrovirus, human T-lymphotropic virus 1 (HTLV-1), was soon associated with an aggressive lymphoma and a chronic inflammatory neurodegenerative disease. Later, other associated clinical manifestations were described, affecting diverse target organs in the human body and showing the enormous burden carried by the virus and the associated diseases. The epidemiology of HTLV-1 and HTLV-2 showed that they were largely distributed around the world, although it is possible to locate geographical areas with pockets of low and very high prevalence and incidence. Aboriginal Australians and indigenous peoples of Brazil are examples of the large spread of HTLV-1 and HTLV-2, respectively. The epidemiological link of both situations is their occurrence among isolated, epidemiologically closed or semi-closed communities. The origin of the viruses in South America shows two different branches with distinct timing of entry. HTLV-1 made its probable entrance in a more recent route through the east coast of Brazil at the beginning of the slave trade from the African continent, starting in the 16th century and lasting for more than 350 years. HTLV-2 followed the ancient route of human migration from the Asian continent, crossing the Behring Strait and then splitting in South America as the population became separated by the Andes Mountains. By that time, HTLV-2c probably arose and became isolated among the indigenous populations in the Brazilian Amazon. The study of epidemiologically closed communities of indigenous populations in Brazil allowed tracing the most likely route of entry, the generation of a new molecular subtype (HTLV-2c), the elucidation of the vertical transmission of HTLV-2, the intrafamilial aggregation of cases and the escape and spread of the virus to other areas in Brazil and abroad. Despite the burden and impact of both viruses, they are maintained as silent infections among human populations because 1, health authorities in most South American countries in which national surveillance is poor have little interest in the disease, 2, the information is commonly lost as indigenous groups do not have specific policies for HTLV and other sexually transmitted infections, and 3, health access is not feasible or properly delivered.

Characterization of pharmacogenetic markers related to Acute Lymphoblastic Leukemia toxicity in Amazonian native Americans population.

Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children. Differences are found among ethnic groups in the results of the treatment of pediatric ALL. In general, children with a high level of native American ancestry tend to respond less positively to ALL treatments, which may be related to specific genomic variants found in native American groups. Despite the evidence, few data are available on the distribution of the pharmacogenomic variants relevant to the treatment of ALL in traditional Amerindian populations, such the those of the Amazon region. Given this, the present study investigated 27 molecular markers related to the treatment of ALL in Amerindians from Brazilian Amazonia and compared the frequencies with those recorded previously on five continents, that are available in the 1,000 Genomes database. The variation in the genotype frequencies among populations was evaluated using Fisher's exact test. The False Discovery Rate method was used to correct the results of the multiple analyses. Significant differences were found in the frequencies of the majority of markers between the Amerindian populations and those of other regions around the world. These findings highlight the unique genetic profile of the indigenous population of Brazilian Amazonia, which may reflect a distinct therapeutic profile for the treatment of ALL in these populations.

Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil.

INTRODUCTION: The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. METHODS: The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. RESULTS: Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. CONCLUSION: Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines.

High prevalence of human T-lymphotropic virus 2 (HTLV-2) infection in villages of the Xikrin tribe (Kayapo), Brazilian Amazon region.

BACKGROUND: Studies have shown that the human T-lymphotropic virus 2 (HTLV-2) is endemic in several indigenous populations of the Brazilian Amazon and molecular analyses have shown the exclusive presence of HTLV-2 subtype 2c among the indigenous groups of this geographical region. METHODS: The present study characterizes the prevalence of HTLV-2 infection in three new villages of the Xikrin tribe, in the Kayapo group, according to their distribution by sex and age. The study included 263 samples from individuals from the Kateté, Djujeko and Oodjã villages. Plasma samples were tested for the presence of anti-HTLV-1/2 antibodies using enzyme-linked immunosorbent assays (ELISA). Seropositive samples were confirmed using real-time PCR, nested PCR and sequencing. RESULTS: The serological and molecular results confirmed the sole presence of HTLV-2 in 77 (29%) samples, with a prevalence of 38% among women and 18% among men. In these communities, it was found that the prevalence of HTLV-2 infection increased with age. Nucleotide sequences (642 bp, 5'LTR) from eight samples were subjected to phylogenetic analysis by the neighbor-joining method to determine the viral subtype, which confirmed the presence of HTLV-2c. CONCLUSIONS: The results of the present study establish the presence of HTLV-2 infection in three new villages of the Xikrin tribe and confirm the high endemicity of the infection in the Kayapo indigenous group of the Brazilian Amazon.

Adesão à terapia antirretroviral de pacientes portadores de HIV/Aids com lipodistrofia / Adherence to antiretroviral therapy by HIV/AIDS patients with lipodystrophy / Adhesión a la terapia antirretroviral de pacientes VIH / SIDA con lipodistrofia

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. Descritores: HIV; AIDS; lipodistrofia; adesão à medicação.

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.

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.

Correction to: Effect of genetic ancestry to the risk of susceptibility to gastric cancer in a mixed population of the Brazilian Amazon.

Following publication of the original article [1], the authors requested a correction to the name of one of the co-authors. The correct name Marianne Rodrigues Fernandes, not Marianne Fernandes Rodrigues.

Effect of genetic ancestry to the risk of susceptibility to gastric cancer in a mixed population of the Brazilian Amazon.

BACKGROUND: Global literature describes differences in the incidence of gastric cancer among populations. For instance, Europeans have lower incidence rates of gastric cancer in relation to Latin and Asian populations, particularly Korean and Japanese populations. However, only a few studies have been able to verify the occurrence of gastric cancer in admixed populations with high interethnic degree mix, such as the Brazilian Amazon region. RESULTS: We observed an increase in European ancestry in the control group compared to the case group (47% vs. 41%). Using increments of 10%, compared to categorical distribution of European ancestry in the sample, we found a difference in the contribution between cases and controls (p = 0.03). Multiple logistic regression was performed to determine the influence of European ancestry in susceptibility to gastric cancer in the sample. According to the adopted model, for each 10% increase in European ancestry, there is a 20% decrease chance of developing gastric cancer (P = 0.0121; OR = 0.81; 95% CI 0.54-0.83). CONCLUSION: Overall, the results suggest that a greater contribution of European ancestry can be a protective factor for the development of gastric cancer in the studied Amazon population. It can help to establish protocols able to predict susceptibility to gastric cancer in admixed populations.

Risco de excesso de peso/gordura corporal e dislipidemias, associadas aos níveis de hemoglobina A2 / Risk of overweight/body fat and dyslipidemia, associated with the levels of hemoglobin A2

Objetivo: estimar o risco do excesso de peso/gordura corporal e dislipidemias, associados aos níveis de hemoglobina A2(HbA2) em população afrodescendente da Amazônia brasileira.Método: estudo analítico transversal,com 182 quilombolas de Trombetas, Pará Brasil, maiores de 20 anos; 41,7% homens e 58,3% mulheres. As variáveis do estudo foram: níveis de HbA2 <2,5%, 2,5-3,5% e >3,5% (variável dependente); medidas antropométricas (Índice de Massa Corporal-IMC, % de Gordura Corporal- BIA; circunferência da cintura ? CC), Colesterol e Triglicerídeo (variáveis independentes). Utilizaram-se médias de tendência central e dispersão, prevalência e teste de associação Qui-quadrado e Odds Ratio, entre as variáveis considerando, separadamente, grupos de acordo com HbA2, para a ocorrência de sobrepeso, excesso de gordura corporal, obesidade abdominal, hipercolesterolemia e hipertrigliceridemia, considerando positivo(?1) e negativo(<1), utilizando o nível de significância 5% (p?0,05). Resultados: para HbA2 <2,5% houve excesso de peso 69,0% sendo, estatisticamente, significante p valor(0,03), excesso de gordura 58,6%, obesidade abdominal 35,7%, hipertrigliceridemia 19,0% e hipercolesterolemia 57,1%. HbA2 2,5-3,5%, as maiores prevalências foram, excesso de peso e hipercolesterolemia (50,4% e 67,8% respectivamente); o risco aumentava para todas as morbidades exceto para hipercolesterolemia. Na HbA2 >3,5%,as maiores prevalências foram a obesidade abdominal e hipertrigliceridemia e os riscos foram menores para essas morbidades. Conclusão: o risco para o excesso de peso passou de 0,49 para 1,42 vezes de chance de ter essas morbidades, em relação aos níveis de concentração de HbA2 <2,5% e >3,5% respectivamente

Objective: estimate the risk of overweight/body fat and dyslipidemias, associated with levels of hemoglobin A2 (HbA2) population of African descents in the Brazilian Amazon. Method: study with 182 African descendent of Trombetas-Pará, more than 20 years, 41.7% men, 58.3% women. Variables: HbA2 categorized as <2.5%, from 2.5 to 3.5% and > 3.5% (low, normal and high, respectively), anthropometric measures (body mass index -BMI, Body Fat %-BIA, Abdominal fat - WC), cholesterol and triglyceride (independent variables). Analysis: means of central tendency and dispersion, prevalence and association test chi-square and the estimated risk (odds ratio) between the variables considering separately the groups according to the levels of HbA2 (dependent variable) for the occurrence of overweight, excess body fat, abdominal obesity, hypercholesterolemia and hypertriglyceridemia (independent variables), considering the positives(?1) ,negatives(<1). Statistical Package for the Social Sciences (SPSS) and in all tests was set the significance level of 5% (p ? 0.05). Results: HbA2 < 2.5% there were prevalence of overweight of 69.0% with a statistically significant p value (0.03), fat excess 58.6%, abdominal obesity 35,7%, hypertriglyceridemia 19.0% and hypercholesterolemia 57.1%. HbA2 2.5-3.5% the highest prevalence were overweight and hypercholesterolemia with 50.4% and 67.8% respectively, while the risk increased for all morbidities except for hypercholesterolemia. HbA2> 3.5%, the highest prevalence were abdominal obesity and hypertriglyceridemia and the risks were lower for these morbidities. Conclusion: however we note that the risk for being overweight increased from 0.49 to 1.42 times likely to have these illnesses when levels of HbA2 increased from <2.5% to> 3.5% respectively.

CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (P450c21, CYP21) accounts for about 95 percent 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 percent of the studied chromosomes. The most common mutations found were IVS2-13A/C > G (36 percent), Q318X (12 percent), V281L (12 percent), 1760_1761insT (9 percent), Cluster E6 (7 percent), and P30L (7 percent). 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.

Prevalence of hereditary risk factors for thrombophilia in Belém, Brazilian Amazon

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 percent) and TAFI T1053C (74 percent) and low frequencies of FVL (1.6 percent), FII G20210A (0.8 percent) and TAFI A152G (0.8 percent). 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.

Frequencies of CCR5-D32, CCR2-64I and SDF1-3A mutations in Human Immunodeficiency Virus (HIV) seropositive subjects and seronegative individuals from the state of Pará in Brazilian Amazonia

The distribution of genetic polymorphisms of chemokine receptors CCR5-D32, CCR2-64I and chemokine (SDF1-3A) 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-D32 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 SDF1-3A 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

Alelos do gene LRP associados ao risco genético da doença de Alzheimer em população exposta ao aluminío / Alleles of the LRP gene associated to the genétic risk of Alzheimer's Disease in population exposed to aluminum

Objetivo:Quantificar os alelos do polimorfismo 766C/T do gene LRP em indivíduos moradores do Lago Batata, expostos à contaminação por Al, e em indivíduos-controle nas comunidades do lago Erepecu e Arancuã pertencentes ao município de oriximiná (Pará). Método: Utilizou-se a técnica de PCR seguida de digestão enzimática com enzima apropriada(Rsal) na análise molecular. Extraiu-se o DNA das amostras de sangue coletadas de 40 moradores do Lago Batata e de 36 indivíduos-controle. Resultados: Em todoas as comunidades, o genótipo C/C e o alelo C mostraram-se os mais comuns, com freqüências superiores a 69 por cento e 80 por cento, respectivamente. Conclusão: A maior prevalência do genótipo C/C pode sugerir a existência de risco genético aumentado para o desenvolvimento da DA. Em relação à população do Lago Batata, particularmente, esse risco pode ser potencializado pela contaminação por alumínio