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Genetic Variants Associated with Arsenic Susceptibility: Study of Purine Nucleoside Phosphorylase, Arsenic (+3) Methyltransferase, and Glutathione S-Transferase Omega Genes

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Title Genetic Variants Associated with Arsenic Susceptibility: Study of Purine Nucleoside Phosphorylase, Arsenic (+3) Methyltransferase, and Glutathione S-Transferase Omega Genes
 
Creator De Chaudhuri, Sujata
Ghosh, Pritha
Sarma, Nilendu
Majumder, Papiya
Sau, Tanmoy Jyoti
Basu, Santanu
Roychoudhury, Susanta
Ray, Kunal
Giri, Ashok K
 
Subject Molecular & Human Genetics
 
Description BACKGROUND: Individual variability in arsenic metabolism may underlie individual susceptibility
toward arsenic-induced skin lesions and skin cancer. Metabolism of arsenic proceeds through
sequential reduction and oxidative methylation being mediated by the following genes: purine
nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), glutathione S-transferase
omega 1 (GSTO1), and omega 2 (GSTO2). PNP functions as arsenate reductase; As3MT methylates
inorganic arsenic and its metabolites; and both GSTO1 and GSTO2 reduce the metabolites.
Alteration in functions of these gene products may lead to arsenic-specific disease manifestations.
OBJECTIVES: To find any probable association between arsenicism and the exonic single nucleotide
polymorphisms (SNPs) of the above-mentioned arsenic-metabolizing genes, we screened all the
exons in those genes in an arsenic-exposed population.
METHODS: Using polymerase chain reaction restriction fragment length polymorphism analysis, we
screened the exons in 25 cases (individuals with arsenic-induced skin lesions) and 25 controls (individuals
without arsenic-induced skin lesions), both groups drinking similar arsenic-contaminated
water. The exonic SNPs identified were further genotyped in a total of 428 genetically unrelated
individuals (229 cases and 199 controls) for association study.
RESULTS: Among four candidate genes, PNP, As3MT, GSTO1, and GSTO2, we found that distribution
of three exonic polymorphisms, His20His, Gly51Ser, and Pro57Pro of PNP, was associated
with arsenicism. Genotypes having the minor alleles were significantly overrepresented in the case
group: odds ratio (OR) = 1.69 [95% confidence interval (CI), 1.08–2.66] for His20His; OR = 1.66
[95% CI, 1.04–2.64] for Gly51Ser; and OR = 1.67 [95% CI, 1.05–2.66] for Pro57Pro.
CONCLUSIONS: The results indicate that the three PNP variants render individuals susceptible
toward developing arsenic-induced skin lesions.
KEY WORDS: arsenic, As3MT, GSTO1, GSTO2, PNP, skin lesion, susceptibility. Environ Health
Perspect 116:501–505 (2008). doi:10.1289/ehp.10581 available via http://dx.doi.org/ [Online
14 January 2008]
 
Date 2008
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1202/1/EHP%2C2008.pdf
De Chaudhuri, Sujata and Ghosh, Pritha and Sarma, Nilendu and Majumder, Papiya and Sau, Tanmoy Jyoti and Basu, Santanu and Roychoudhury, Susanta and Ray, Kunal and Giri, Ashok K (2008) Genetic Variants Associated with Arsenic Susceptibility: Study of Purine Nucleoside Phosphorylase, Arsenic (+3) Methyltransferase, and Glutathione S-Transferase Omega Genes. Environmental Health Perspectives, 116 (4).
 
Relation http://dx.doi.org/
http://www.eprints.iicb.res.in/1202/