Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions.
OBJECTIVE
We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships.


METHODS
A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan.


RESULTS
A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate] was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary methylation ratios.


CONCLUSIONS
Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals.
McCarty
Kathleen M
KM
Yale University School of Medicine, Epidemiology and Public Health, Division of Environmental Health Sciences, New Haven, Connecticut 06520, USA. Kathleen.McCarty@yale.edu
Chen
Yen-Ching
YC
Quamruzzaman
Quazi
Q
Rahman
Mahmuder
M
Mahiuddin
Golam
G
Hsueh
Yu-Mei
YM
Su
Li
L
Smith
Thomas
T
Ryan
Louise
L
Christiani
David C
DC
D000328:Adult; D001149:Arsenates / Q000652:urine; D001151:Arsenic / Q000032:analysis / Q000652:urine*; D001152:Arsenicals / Q000652:urine; D018053:Arsenites / Q000652:urine; D001459:Bangladesh / Q000453:epidemiology; D002101:Cacodylic Acid / Q000031:analogs & derivatives / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008745:Methylation; D009262:Nails / Q000737:chemistry; D011110:Polymorphism, Genetic; D012871:Skin Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000652:urine*; D014881:Water Supply / Q000032:analysis
D001149:Arsenates; D001151:Arsenic; D001152:Arsenicals; D018053:Arsenites; D002101:Cacodylic Acid; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D014874:Water Pollutants, Chemical; C472511:dimethylarsinous acid; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C020300:monomethylarsonic acid; C015001:arsenite; C025657:arsenic acid