A case-control study of GST polymorphisms and arsenic related skin lesions.
BACKGROUND
Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. Individual factors in arsenic biotransformation may influence disease susceptibility. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates.


METHODS
We investigated whether polymorphisms in GSTT1, GSTP1 and GSTM1 were associated with risk of skin lesions and whether these polymorphisms modify the relationship between drinking water arsenic exposure and skin lesions in a case control study of 1200 subjects frequency matched on age and gender in community clinics in Pabna, Bangladesh in 2001-2002.


CONCLUSIONS
GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status (OR1.56 95% CI 1.10-2.19). The GSTP1 GG polymorphism was associated with greater odds of skin lesions compared to GSTP1 AA, (OR 1.86 (95%CI 1.15-3.00). No evidence of effect modification by GSTT1, GSTM1 or GSTP1 polymorphisms on the association between arsenic exposure and skin lesions was detected.


CONCLUSIONS
GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions.
McCarty
Kathleen M
KM
Yale University School of Medicine, Epidemiology and Public Health, Division of Environmental Health Sciences, New Haven, CT, USA. kmccarty@hohp.harvard.edu
Ryan
Louise
L
Houseman
E Andres
EA
Williams
Paige L
PL
Miller
David P
DP
Quamruzzaman
Quazi
Q
Rahman
Mahmuder
M
Mahiuddin
Golam
G
Smith
Thomas
T
Gonzalez
Ernesto
E
Su
Li
L
Christiani
David C
DC
D000293:Adolescent; D000328:Adult; D001151:Arsenic / Q000032:analysis; D020261:Arsenic Poisoning / Q000175:diagnosis / Q000453:epidemiology*; D016022:Case-Control Studies; D015984:Causality; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D014881:Water Supply / Q000032:analysis
D001151:Arsenic; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human