McCarty Kathleen M, Ryan Louise, Houseman E Andres, Williams Paige L, Miller David P, Quamruzzaman Quazi, Rahman Mahmuder, Mahiuddin Golam, Smith Thomas, Gonzalez Ernesto, Su Li, Christiani David C
Yale University School of Medicine, Epidemiology and Public Health, Division of Environmental Health Sciences, New Haven, CT, USA.
Environ Health. 2007 Feb 6;6:5. doi: 10.1186/1476-069X-6-5.
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.
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.
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.
GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions.
谷胱甘肽S-转移酶T1(GSTT1)、谷胱甘肽S-转移酶M1(GSTM1)和谷胱甘肽S-转移酶P1(GSTP1)基因多态性会影响谷胱甘肽S-转移酶对致癌物的解毒作用,据报道这些多态性会增加对环境相关健康结局的易感性。砷生物转化中的个体因素可能影响疾病易感性。谷胱甘肽S-转移酶活性参与内源性和外源性化合物的代谢,包括催化砷与谷胱甘肽结合物的形成。
在2001 - 2002年于孟加拉国帕布纳社区诊所开展的一项病例对照研究中,我们调查了GSTT1、GSTP1和GSTM1基因多态性是否与皮肤病变风险相关,以及这些多态性是否会改变饮用水砷暴露与皮肤病变之间的关系。该研究纳入了1200名年龄和性别频率匹配的受试者。
与纯合缺失状态相比,GSTT1纯合野生型状态与皮肤病变几率增加相关(比值比1.56,95%置信区间1.10 - 2.19)。与GSTP1 AA相比,GSTP1 GG多态性与更高的皮肤病变几率相关(比值比1.86(95%置信区间1.15 - 3.00)。未检测到GSTT1、GSTM1或GSTP1基因多态性对砷暴露与皮肤病变之间关联的效应修饰作用。
GSTT1野生型和GSTP1 GG与皮肤病变风险增加相关。