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Genetic Polymorphism of Delta Aminolevulinic Acid Dehydratase (ALAD) Gene and Symptoms of Chronic Mercury Exposure in Munduruku Indigenous Children within the Brazilian Amazon.

ABSTRACT: Genetic polymorphisms involved in mercury toxicokinetics and toxicodynamics may be associated with severe mercury toxicity. This study aimed to investigate the impact of an ALAD polymorphism on chronic mercury exposure and the health situation of indigenous children from the Brazilian Amazon. One-hundred-and-three indigenous children (under 15 years old) were included and genotyped (rs1800435) using a TaqMan validated assay. The mean age was 6.6 ± 4.5 years old, 60% were female, 49% presented with anemia, and the mean hair mercury concentration was 7.0 ± 4.5 (1.4-23.9) µg/g, with 49% exceeding the reference limit (≥6.0 µg/g). Only two children were heterozygous ALAD, while the others were all wild type. Minor allele frequency (ALAD G) and heterozygous genotype (ALAD CG) were 1% and 2%, respectively. The two children (12 and 14 years old) with the ALAD polymorphism had mercury levels above the average as well as had neurological symptoms related to chronic mercury exposure, such as visual field alterations, memory deficit, distal neuropathy, and toe amyotrophy. Both children also reported frequent consumption of fish in the diet, at least three times a week. In conclusion, our data confirm that an ALAD polymorphism can contribute to mercury half-life time, harmful effects, and neuropsychological disorders in indigenous children with chronic mercury exposure to gold mining activity.

SUBMITTER: Perini JA

PROVIDER: S-EPMC8394242 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The Amazonian indigenous peoples depend on natural resources to live, but human activities' growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 μg/g, with significant differences between the villages (Kruskal-Wallis test: 19.9; p-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0-1.8), high blood pressure (PR: 1.6; CI95%: 1.3-2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3-2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2-2.3), with pregnancy (PR: 1.5; CI95%: 1.0-2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0-3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4-4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.

Project description:ObjectiveTo determine whether a polymorphism the in delta-aminolevulinic acid dehydratase (ALAD) gene modifies the neurotoxicity of lead in older adults.MethodsThe authors studied men participating in the Department of Veterans Affairs' Normative Aging Study, assessing their recent exposure to lead by measuring blood lead (n = 915) at each triennial clinic visit, and, beginning in 1991, assessing their cumulative exposure by measuring lead levels in tibia (n = 722) and patella (n = 720), using K-shell x ray fluorescence. Starting in 1993 and again at each triennial visit, the authors administered the Mini-Mental State Examination (MMSE) to assess their cognitive functioning. The relation of the lead biomarkers to MMSE score was evaluated and this association was compared among men who carried the variant allele, ALAD-2, versus men without the allele.ResultsSixteen per cent of men carried the ALAD-2 allele. Median tibia and patella lead levels (first-third quartile) were 19 (13-28) and 27 (18-39) microg/g. Blood lead levels were consistent with non-occupational exposure: only 6% of men had levels > or =10 microg/dl. In multivariable adjusted analyses, higher levels of blood lead were associated with poorer performance on the MMSE. This association was most pronounced among ALAD-2 carriers, among whom a 3 microg/dl increment in blood lead (the interquartile range) was associated with a 0.26 point lower mean MMSE score (95% CI -0.54 to 0.01), compared with a 0.04 point lower score (95% CI -0.16 to 0.07) among non-carriers. The modest 0.22 point difference in these associations did not attain statistical significance, however (p(interaction) = 0.13). The associations between bone lead levels and MMSE score did not vary by ALAD-2 status.ConclusionsAlthough not statistically significant, these findings suggest that ALAD genotype may modify blood lead's adverse association with cognition among older men who had community exposures to lead. However, despite a relatively large sample size and the use of sensitive methods for measuring lead burden, the evidence overall was fairly weak.

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Genetic Polymorphism of Delta Aminolevulinic Acid Dehydratase (ALAD) Gene and Symptoms of Chronic Mercury Exposure in Munduruku Indigenous Children within the Brazilian Amazon.

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