Abstract
BackgroundPolymorphisms 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.MethodsWe 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.Results and discussionGSTT1 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.ConclusionGSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions.
Highlights
Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by Glutathione S-transferases (GST) and have been reported to increase susceptibility to environmentally related health outcomes
We investigated the relationship between GSTT1, GSTM1, and GSTP1 polymorphisms and skin lesions
We found that GSTT1 wildtype compared to GSTT1 null, and GSTP1 GG compared to GSTP1 AA were associated with an increased odds of arsenic related skin lesions
Summary
Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates. Glutathione S-transferases (GST) are a superfamily of enzymes that are key in the detoxification step of Phase II metabolism, usually by catalyzing the conjugation of reduced glutathione (GSH) into hydrophobic and electrophilic compounds along with other Phase II enzymes [10,11,12]. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenicGSH conjugates[13,14]. Chronic arsenic exposure has been shown to alter glutathione metabolism and cellular redox status and maintenance of cellular redox state may have an important role in arsenic related pathology[14,18,19]
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