Indigenous American Ancestry is Associated with arsenic methylation efficiency in an admixed population of northwest Mexico

Paulina Gomez-Rubio, Yann C Klimentidis, Ernesto Cantu-Soto, Maria M. Meza-Montenegro, David D Billheimer, Zhenqiang Lu, Zhao Chen, Walter Klimecki

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 μg/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.

Original languageEnglish (US)
Pages (from-to)36-49
Number of pages14
JournalJournal of Toxicology and Environmental Health - Part A: Current Issues
Volume75
Issue number1
DOIs
StatePublished - 2012

Fingerprint

Methylation
Arsenic
Mexico
Population
Body Mass Index
Association reactions
Epidemiology
Poisons
Proxy
Metabolites
Genetic Markers
Haplotypes
Epidemiologic Studies

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Toxicology

Cite this

@article{2b87aaeaf7b44576b758a8e4fec68907,
title = "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 μg/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.",
author = "Paulina Gomez-Rubio and Klimentidis, {Yann C} and Ernesto Cantu-Soto and Meza-Montenegro, {Maria M.} and Billheimer, {David D} and Zhenqiang Lu and Zhao Chen and Walter Klimecki",
year = "2012",
doi = "10.1080/15287394.2011.615107",
language = "English (US)",
volume = "75",
pages = "36--49",
journal = "Journal of Toxicology and Environmental Health - Part A: Current Issues",
issn = "1528-7394",
publisher = "Taylor and Francis Ltd.",
number = "1",

}

TY - JOUR

T1 - Indigenous American Ancestry is Associated with arsenic methylation efficiency in an admixed population of northwest Mexico

AU - Gomez-Rubio, Paulina

AU - Klimentidis, Yann C

AU - Cantu-Soto, Ernesto

AU - Meza-Montenegro, Maria M.

AU - Billheimer, David D

AU - Lu, Zhenqiang

AU - Chen, Zhao

AU - Klimecki, Walter

PY - 2012

Y1 - 2012

N2 - 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 μg/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.

AB - 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 μg/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.

UR - http://www.scopus.com/inward/record.url?scp=81255209126&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81255209126&partnerID=8YFLogxK

U2 - 10.1080/15287394.2011.615107

DO - 10.1080/15287394.2011.615107

M3 - Article

C2 - 22047162

AN - SCOPUS:81255209126

VL - 75

SP - 36

EP - 49

JO - Journal of Toxicology and Environmental Health - Part A: Current Issues

JF - Journal of Toxicology and Environmental Health - Part A: Current Issues

SN - 1528-7394

IS - 1

ER -