Li R, Boerwinkle E, Olshan A F, Chambless L E, Pankow J S, Tyroler H A, Bray M, Pittman G S, Bell D A, Heiss G
Department of Epidemiology, University of North Carolina at Chapel Hill, Suite 306, NationsBank Plaza, 137 E. Franklin Street, Chapel Hill, NC 27514, USA.
Atherosclerosis. 2000 Apr;149(2):451-62. doi: 10.1016/s0021-9150(99)00483-9.
Cancer studies suggest that the null polymorphisms of glutathione S-transferase M1 or T1 (GSTM1/GSTT1) may affect the ability to detoxify or activate chemicals in cigarette smoke. The potential modification of the association between smoking and coronary heart disease (CHD) by GSTM1 and GSTT1 has not been studied in humans. A case-cohort study was conducted to test the hypotheses that specific genotypes of GSTM1 or GSTT1 affect susceptibility to smoking-related CHD. CHD cases (n=400) accrued during 1987-1993 and a cohort-representative sample (n=924) were selected from a biracial cohort of 15792 middle-aged men and women in four US communities. A significantly higher frequency of GSTM1-0 and a lower frequency of GSTT1-0 were found in whites (GSTM1-0=47.1%, GSTT1-0=16.4%) than in African-Americans (AAs) (GSTM1-0=17.5%, GSTT1-0=25.9%). A smoking-GSTM1-0 interaction for the risk of CHD was statistically significant on an additive scale, with ever-smokers with GSTM1-0 at a approximately 1.5-fold higher risk relative to ever-smokers with GSTM1-1 and a approximately 2-fold higher risk relative to never-smokers with GSTM1-0, after adjustment for other CHD risk factors. The interaction between having smoked >/=20 pack-years and GSTT1-1 was statistically significant on both multiplicative and additive scales. The risk of CHD given both GSTT1-1 and >/=20 pack-years of smoking was approximately three times greater than the risk given exposure to >/=20 pack-years of smoking alone, and approximately four times greater than the risk given exposure to GSTT1-1 alone. The modification of the smoking-CHD association by GSTM1 or GSTT1 suggests that chemicals in cigarette smoke that are substrates for glutathione S-transferases may be involved in the etiology of CHD.
癌症研究表明，谷胱甘肽S-转移酶M1或T1（GSTM1/GSTT1）的无效多态性可能会影响对香烟烟雾中化学物质的解毒或激活能力。GSTM1和GSTT1对吸烟与冠心病（CHD）之间关联的潜在影响尚未在人类中进行研究。开展了一项病例队列研究，以检验GSTM1或GSTT1的特定基因型会影响与吸烟相关的冠心病易感性这一假设。从美国四个社区的15792名中年男女的双种族队列中，选取了1987年至1993年期间确诊的冠心病病例（n = 400）以及队列代表性样本（n = 924）。白人中GSTM1-0的频率显著更高，GSTT1-0的频率更低（GSTM1-0 = 47.1%，GSTT1-0 = 16.4%），而非裔美国人（AAs）中GSTM1-0 = 17.5%，GSTT1-0 = 25.9%。在调整其他冠心病危险因素后，GSTM1-0与吸烟对冠心病风险的相互作用在相加尺度上具有统计学意义，GSTM1-0的曾经吸烟者相对于GSTM1-1的曾经吸烟者患冠心病的风险高出约1.5倍，相对于GSTM1-0的从不吸烟者高出约2倍。吸烟≥20包年与GSTT1-1之间的相互作用在相乘和相加尺度上均具有统计学意义。同时存在GSTT1-1且吸烟≥20包年时患冠心病的风险约为仅吸烟≥20包年时风险的三倍，约为仅存在GSTT1-1时风险的四倍。GSTM1或GSTT1对吸烟与冠心病关联的影响表明，作为谷胱甘肽S-转移酶底物的香烟烟雾中的化学物质可能参与了冠心病的病因。
