title: Genetic variants associated with arsenic susceptibility: study of purine nucleoside phosphorylase, arsenic (+3) methyltransferase, and glutathione S-transferase omega genes.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Sujata
authors.initials: S
authors.lastname: De Chaudhuri
authors.forename: Pritha
authors.initials: P
authors.lastname: Ghosh
authors.forename: Nilendu
authors.initials: N
authors.lastname: Sarma
authors.forename: Papiya
authors.initials: P
authors.lastname: Majumdar
authors.forename: Tanmoy Jyoti
authors.initials: TJ
authors.lastname: Sau
authors.forename: Santanu
authors.initials: S
authors.lastname: Basu
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Giri
mesh_terms: D000328:Adult; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics*; D012871:Skin Diseases / Q000139:chemically induced / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D008780:Methyltransferases; C505756:AS3MT protein, human; D011683:Purine-Nucleoside Phosphorylase; C490476:GSTO1 protein, human; C492569:GSTO2 protein, human; D005982:Glutathione Transferase; D001151:Arsenic