Differential distribution of NAT2 polymorphisms and NAT2 acetylator phenotypes among indigenous populations of the Brazilian Amazon.

OBJECTIVES: We report, for the first time, the distribution of four no-function NAT2 single nucleotide polymorphisms and inferred NAT2 acetylator phenotypes in three indigenous groups (Munduruku, Paiter-Suruí, and Yanomami), living in reservation areas in the Brazilian Amazon. METHODS: Two hundred and seventy-six participants from three indigenous groups (92 for each group) were included and genotyped for four NAT2 polymorphisms (rs1801279, rs1801280, rs1799930, and rs1799931) by the TaqMan system. Minor Allele Frequency (MAF) was determined and NAT2 acetylator phenotypes were inferred. RESULTS: NAT2 rs1801279G>A was absent in all cohorts; rs1799930G>A was absent in Yanomami and rare (MAF 0.016) in Munduruku and Paiter-Suruí; MAF of rs1801280T>C ranged five-fold (0.092-0.433), and MAF of rs1799931G>A varied between 0.179 and 0.283, among the three groups. The distribution of NAT2 phenotypes differed significantly across cohorts; the prevalence of the slow acetylator phenotype ranged from 16.3% in Yanomami to 33.3% in Munduruku to 48.9% in Paiter-Suruí. This three-fold range of variation is of major clinical relevance because the NAT2 slow phenotype is associated with higher risk of hepatotoxicity with antituberculosis chemotherapy and high incidence rates of tuberculosis and burden of latent infection among Munduruku, Paiter-Surui, and Yanomami peoples. According to the frequency of the NAT2 slow acetylator phenotype, the estimated number of individuals needed to be genotyped to prevent one additional event of hepatotoxicity range from 31 (Munduruku) to 39 (Paiter-Surui) and to 67 (Yanomami). CONCLUSION: The rs1801279 polymorphism was not found in any of the cohorts, while the MAF of the other polymorphisms showed significant variation between the cohorts. The difference in the prevalence of the NAT2 slow acetylator phenotype, which is linked to isoniazid-induced hepatotoxicity, was observed in the different study cohorts.

Long-Term Environmental Methylmercury Exposure Is Associated with Peripheral Neuropathy and Cognitive Impairment among an Amazon Indigenous Population.

Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 µg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, p = 0.010) and 95.9% (95%CI 16-230.8%, p = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.

Human Mercury Exposure in Yanomami Indigenous Villages from the Brazilian Amazon.

In the Brazilian Amazon, where the majority of Yanomami villages are settled, mercury (Hg) exposure due to artisanal small-scale gold mining (ASGM) has been reported since the 1980s. This study assessed mercury exposure in the Yanomami reserve and whether the level of contamination was related to the ASGM geographical location. It was conducted using a cross-sectional study of 19 villages. Direct interviews were performed and hair samples were used as a bioindicator of Hg exposure. The Prevalence-Ratio (PR) was estimated as an indicator of association between ASGM geographical locations and human exposure to mercury. Mercury levels (239 hair samples) ranged between 0.4 and 22.1 µg·g-1 and presented substantial differences amongst the villages. In the Waikas-Aracaça region, where current ASGM was reported, we observed the highest Hg concentrations (median = 15.5 µg·g-1). Almost all participants presented with hair-Hg levels >6 µg·g-1 (prevalence = 92.3%). In the Paapiu region, we observed the lowest concentrations (median = 3.2 µg·g-1; prevalence = 6.7%). Our findings showed that the Waikas Ye'kuana and Waikas Aracaca villages presented with 4.4 (PR = 4.4; Confidence Interval (CI) 95% = 2.2⁻9.0) and 14.0 (PR = 14.0; CI 95% = 7.9⁻24.9) times higher prevalence of hair-Hg concentration, respectively, compared with Paapiu. Considering seasonal variation of Hg-exposure, the lowest concentrations were observed during the wet season (June⁻September) and the highest in the dry season (December⁻April). Our study suggests that there is an association between mercury exposure and ASGM geographical locations.

The burden of tuberculosis in indigenous peoples in Amazonia, Brazil.

Tuberculosis (TB) stands out as one of the principal infectious diseases affecting Amazonian Indians. Recent research indicates that incidence rates among indigenous peoples may be as much as ten times higher than those of the general Brazilian population. Purified protein derivative reactivity in Amazonia is low compared with populations of European descent; anergy rates usually surpass 50%, even under high BCG coverage. An annual risk of infection of 1.2-2.2% points to high rates of transmission. Whether or not particular susceptibility to TB is linked to genetics, Amazonian Indians face a disproportionately high risk of contracting and dying from TB.

Spatial-temporal trends and risk of suicide in Central Brazil: an ecological study contrasting indigenous and non-indigenous populations.

OBJECTIVE: To examine spatial-temporal distribution and risk of suicide, as well as trends in suicide mortality rates, in the indigenous and non-indigenous population of the state of Mato Grosso do Sul, Brazil. METHODS: Data were obtained from the Information Department of the Brazilian Unified Health System. Deaths recorded as voluntary self-inflicted injuries (ICD-10 codes X60.0 to X84.9) were considered suicide. Suicide rates were estimated and adjusted by age in the population > 9 years of age. Kernel analysis was used to assess the spatial distribution of suicide cases, while trend analysis was carried out using a non-parametric test (Mann-Kendall). RESULTS: The suicide risk among the indigenous population was 8.1 (95%CI 7.2-9.0) times higher than in the non-indigenous population. For indigenous residents in the 15-24 age group, the risk was 18.5 (95%CI 17.5-19.6) times higher than in the non-indigenous population. The majority of indigenous cases were concentrated in a few villages in reservation areas, mainly occupied by Guarani-Kaiowá and Guarani-Ñandeva groups. Rate patterns remained stable over time in both groups. CONCLUSION: Suicide is a serious public health problem in Mato Grosso do Sul, and has had an alarming and disproportionate impact on the indigenous population for more than a decade.

Factors associated with anti-TB drug-induced hepatotoxicity and genetic polymorphisms in indigenous and non-indigenous populations in Brazil.

Anti-tuberculosis (TB) drugs are responsible for the occurrence of several adverse drug reactions (ADRs), including hepatotoxicity. The aim was to estimate the incidence of hepatotoxicity and its association with genetic polymorphisms and clinical-epidemiological factors by comparing indigenous and non-indigenous TB patients. We investigated clinical-epidemiological variables, serum levels of liver enzymes and NAT2, CYP2E1 and GSTM1 polymorphisms. A non-conditional logistic regression was used to identify the factors associated with hepatotoxicity. Odds ratios were used as the association measures. The incidence of hepatotoxicity was 19.7% for all patients. The risk of hepatotoxicity was almost four times higher in indigenous patients, comparing to non-indigenous. We identified a new nonsynonymous single nucleotide polymorphism of NAT2 in indigenous patients. In total, 54.6% of the patients expressed a slow acetylation phenotype profile. The frequency of the null genotype of GSTM1 was higher in non-indigenous patients (p = 0.002), whereas no significant differences in relation to polymorphisms of CYP2E1 were observed between the groups. Hepatotoxicity was associated with patients older than 60 and indigenous (OR = 26.0; 95%CI:3.1-217.6; OR = 3.8; 95%CI:1.3-11.1, respectively). Furthermore, hepatotoxicity was associated with a slow acetylation profile in indigenous patients (OR = 10.7; 95%CI:1.2-97.2). Our findings suggest that there are distinct acetylation profiles in the Brazilian population, emphasizing the importance of pharmacogenetic analyses for achieving personalized therapeutic schemes and better outcomes.

Spatial-temporal trends and risk of suicide in Central Brazil: an ecological study contrasting indigenous and non-indigenous populations

Objective: To examine spatial-temporal distribution and risk of suicide, as well as trends in suicide mortality rates, in the indigenous and non-indigenous population of the state of Mato Grosso do Sul, Brazil. Methods: Data were obtained from the Information Department of the Brazilian Unified Health System. Deaths recorded as voluntary self-inflicted injuries (ICD-10 codes X60.0 to X84.9) were considered suicide. Suicide rates were estimated and adjusted by age in the population > 9 years of age. Kernel analysis was used to assess the spatial distribution of suicide cases, while trend analysis was carried out using a non-parametric test (Mann-Kendall). Results: The suicide risk among the indigenous population was 8.1 (95%CI 7.2-9.0) times higher than in the non-indigenous population. For indigenous residents in the 15-24 age group, the risk was 18.5 (95%CI 17.5-19.6) times higher than in the non-indigenous population. The majority of indigenous cases were concentrated in a few villages in reservation areas, mainly occupied by Guarani-Kaiowá and Guarani-Ñandeva groups. Rate patterns remained stable over time in both groups. Conclusion: Suicide is a serious public health problem in Mato Grosso do Sul, and has had an alarming and disproportionate impact on the indigenous population for more than a decade.

Cytokine genes are associated with tuberculin skin test response in a native Brazilian population.

Tuberculosis was a major cause of population decline among Brazilian indigenous peoples and remains a leading cause of morbidity and mortality among them. Despite high BCG coverage, results of Tuberculin Skin Test (TST) reactivity have shown high rates of anergy in Amazonian Indians. Given the high prevalence of anergy in these populations and the fact that genetic host factors play an important role in susceptibility to Mycobacterium tuberculosis (MTB), the aim of this study was to evaluate the association of nineteen polymorphisms in fifteen genes related to immune response and anergy in the Xavante, an indigenous group from Brazil. A total of 481 individuals were investigated. TST anergy was observed in 69% of them. Polymorphisms in four genes showed absence or very low variability: SP110, PTPN22, IL12RB1 and IL6. IFNG +874 A/T heterozygotes and IL4-590 C/C homozygotes were more frequent in those individuals who presented a positive TST (prevalence ratios of 1.9 and 2.0 respectively). The risk of anergy was 1.5 in IL10-1082 G/G homozygotes when compared to carriers for the A allele. In indigenous groups such as the Xavante exposure to a variety of infections, associated with specific genetic factors, may disturb the T-helper 1 and T-helper 2 balance leading to increased immunological susceptibility.