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ABSTRACT: Background
Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal.Methods
Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls.Results
Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62).Conclusions
We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.
SUBMITTER: Pierce BL
PROVIDER: S-EPMC3887566 | biostudies-literature | 2013 Dec
REPOSITORIES: biostudies-literature
Pierce Brandon L BL Tong Lin L Argos Maria M Gao Jianjun J Farzana Jasmine J Roy Shantanu S Paul-Brutus Rachelle R Rahaman Ronald R Rakibuz-Zaman Muhammad M Parvez Faruque F Ahmed Alauddin A Quasem Iftekhar I Hore Samar K SK Alam Shafiul S Islam Tariqul T Harjes Judith J Sarwar Golam G Slavkovich Vesna V Gamble Mary V MV Chen Yu Y Yunus Mohammad M Rahman Mahfuzar M Baron John A JA Graziano Joseph H JH Ahsan Habibul H
International journal of epidemiology 20131201 6
<h4>Background</h4>Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesi ...[more]