Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Feb;117(2):254-60.
doi: 10.1289/ehp.11872. Epub 2008 Sep 26.

Folate deficiency, hyperhomocysteinemia, low urinary creatinine, and hypomethylation of leukocyte DNA are risk factors for arsenic-induced skin lesions

J Richard Pilsner  1 , Xinhua Liu, Habibul Ahsan, Vesna Ilievski, Vesna Slavkovich, Diane Levy, Pam Factor-Litvak, Joseph H Graziano, Mary V Gamble
Affiliations

Folate deficiency, hyperhomocysteinemia, low urinary creatinine, and hypomethylation of leukocyte DNA are risk factors for arsenic-induced skin lesions

J Richard Pilsner et al. Environ Health Perspect. 2009 Feb.

Abstract

Background: Arsenic methylation relies on folate-dependent one-carbon metabolism and facilitates urinary As elimination. Clinical manifestations of As toxicity vary considerably among individuals and populations, and poor methylation capacity is thought to confer greater susceptibility.

Objective: After determining that folate deficiency, hyperhomocysteinemia, and low urinary creatinine are associated with reduced As methylation, and that As exposure is associated with increased genomic methylation of leukocyte DNA, we asked whether these factors are associated with As-induced skin lesion risk among Bangladeshi adults.

Methods: We conducted a nested case-control study of 274 cases who developed lesions 2 years after recruitment, and 274 controls matched to cases for sex, age, and water As.

Results: The odds ratios and 95% confidence intervals (CIs) for development of skin lesions for participants who had low folate (< 9 nmol/L), hyperhomocysteinemia (men, > 11.4 micromol/L; women, > 10.4 micromol/L), or hypomethylated leukocyte DNA at recruitment (< median) were 1.8 (95% CI, 1.1-2.9), 1.7 (95% CI, 1.1-2.6), and 1.8 (95% CI, 1.2-2.8), respectively. Compared with the subjects in the first quartile, those in the third and fourth quartiles for urinary creatinine had a 0.4-fold decrease in the odds of skin lesions (p < 0.01).

Conclusions: These results suggest that folate deficiency, hyperhomocysteinemia, and low urinary creatinine, each associated with decreased As methylation, are risk factors for As-induced skin lesions. The increased DNA methylation associated with As exposure previously observed, and confirmed among controls in this study, may be an adaptive change because hypomethylation of leukocyte DNA is associated with increased risk for skin lesions.

Keywords: Bangladesh; DNA methylation; arsenic; epigenetics; folate; folate deficiency; global methylation; homocysteine; hyperhomocysteinemia; skin lesions.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahsan H, Chen Y, Kibriya MG, Slavkovich V, Parvez F, Jasmine F, et al. Arsenic metabolism, genetic susceptibility, and risk of premalignant skin lesions in Bangladesh. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1270–1278. - PubMed
    1. Ahsan H, Chen Y, Parvez F, Argos M, Hussain AI, Momotaj H, et al. Health Effects of Arsenic Longitudinal Study (HEALS): description of a multidisciplinary epidemiologic investigation. J Expo Sci Environ Epidemiol. 2006a;16(2):191–205. - PubMed
    1. Ahsan H, Chen Y, Parvez F, Zablotska L, Argos M, Hussain I, et al. Arsenic exposure from drinking water and risk of premalignant skin lesions in Bangladesh: baseline results from the Health Effects of Arsenic Longitudinal Study. Am J Epidemiol. 2006b;163(12):1138–1148. - PubMed
    1. Ahsan H, Perrin M, Rahman A, Parvez F, Stute M, Zheng Y, et al. Associations between drinking water and urinary arsenic levels and skin lesions in Bangladesh. J Occup Environ Med. 2000;42(12):1195–1201. - PubMed
    1. Bagchi S. Arsenic threat reaching global dimensions. Canadian Med Assn J. 2007;177(11):1344–1345. - PMC - PubMed

Publication types

-