Dataset Information

Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico.

ABSTRACT: Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high percent urinary monomethylarsonic acid (MMA(V)), with several As-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic As metabolite. Some epidemiological studies suggested that indigenous Americans (AME) methylate As more efficiently; however, data supporting this have been equivocal. The aim of this study was to characterize the association between AME ancestry and As methylation efficiency using a panel of ancestry informative genetic markers to determine individual ancestry proportions in an admixed population (composed of two or more isolated ancestral populations) of 746 individuals environmentally exposed to As in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3-1053.5 ?g/L, while percent AME (%AME) mean and range were 72.4 and 23-100. Adjusted (gender, age, AS3MT 7388/M287T haplotypes, body mass index [BMI], and TAs) multiple regression model showed that higher AME ancestry is significantly associated with lower percentage of urinary As excreted as MMA(V) (%uMMA) in this population (p < .01). Data also demonstrated a significant interaction between BMI and gender, indicating negative association between BMI and %uMMA, stronger in women than men (p < .01). Moreover, age and the AS3MT variants 7388 (intronic) and M287T (nonsynonymous) were also significantly associated with As methylation efficiency (p < .01). This study highlights the importance of BMI and indigenous American ancestry in some of the observed variability in As methylation efficiency, underscoring the need to be considered in epidemiology studies, particularly those carried out in admixed populations.

SUBMITTER: Gomez-Rubio P

PROVIDER: S-EPMC3572940 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico.

Gomez-Rubio Paulina P Klimentidis Yann C YC Cantu-Soto Ernesto E Meza-Montenegro Maria M MM Billheimer Dean D Lu Zhenqiang Z Chen Zhao Z Klimecki Walter T WT

Journal of toxicology and environmental health. Part A 20120101 1

Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high percent urinary monomethylarsonic acid (MMA(V)), with several As-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic As metabolite. Some epidemiological studies suggested that indigenous Americans (AME) methylate As more efficiently; however, data supporting this have been equivocal. The aim of this study was to characterize the association ...[more]

PMID: 22047162

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Project description:Ancestry informative markers (AIMs) are used in forensic genetics to infer biogeographical ancestry (BGA) of individuals and may also have a prominent role in future police and identification investigations. In the last few years, many studies have been published reporting new AIM sets. These sets include markers (usually around 100 or less) selected with different purposes and different population resolutions. Regardless of the ability of these sets to separate populations from different continents or regions, the uncertainty associated with the estimates provided by these panels and their capacity to accurately report the different ancestral contributions in individuals of admixed populations has rarely been investigated. This issue is addressed in this study by evaluating different AIM sets. Ancestry inference was carried out in admixed South American populations, both at population and individual levels. The results of ancestry inferences using AIM sets with different numbers of markers among admixed reference populations were compared. To evaluate the performance of the different ancestry panels at the individual level, expected and observed estimates among families and their offspring were compared, considering that (1) the apportionment of ancestry in the offspring should be closer to the average ancestry of the parents, and (2) full siblings should present similar ancestry values. The results obtained illustrate the importance of having a good balance/compromise between not only the number of markers and their ability to differentiate ancestral populations, but also a balanced differentiation among reference groups, to obtain more precise values of genetic ancestry. This work also highlights the importance of estimating errors associated with the use of a limited number of markers. We demonstrate that although these errors have a moderate effect at the population level, they may have an important impact at the individual level. Considering that many AIM-sets are being described for inferences at the individual level and not at the population level, e.g., in association studies or the determination of a suspect's BGA, the results of this work point to the need of a more careful evaluation of the uncertainty associated with the ancestry estimates in admixed populations, when small AIM-sets are used.

Dataset Information

Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico.

Publications

Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico.

Similar Datasets

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