Miller Eric A, Pankow James S, Millikan Robert C, Bray Molly S, Ballantyne Christie M, Bell Douglas A, Heiss Gerardo, Li Rongling
Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
Atherosclerosis. 2003 Dec;171(2):265-72. doi: 10.1016/j.atherosclerosis.2003.07.007.
Recent epidemiologic studies suggest that polymorphisms of glutathione-S-transferases M1 and T1 (GSTM1/GSTT1) modify the effects of cigarette smoking on risk of coronary heart disease (CHD). Since GSTs are able to detoxify numerous toxic compounds and products of oxidative stress, it is possible that GST genotypes may also modify the capacity of smoking to invoke a chronic inflammatory response. A cross-sectional analysis, using a subset of participants (n = 989) in a large (n = 15, 792) biracial cohort, was used to evaluate levels of nine markers of inflammation, hemostasis, and endothelial function by different combinations of GST genotypes and cigarette smoking status. Participants with the GSTM1 null (GSTM1-0) genotype and > or = 20 pack-years of smoking had the highest mean levels of CRP, fibrinogen, von Willebrand factor, ICAM-1, and VCAM-1 and lowest mean levels of albumin compared to other combinations of genotype and smoking. However, a formal test for interaction between GSTM1 genotype and smoking was statistically significant only for albumin. By contrast, participants who had the functional GSTT1 genotype (GSTT1-1) and smoked > or = 20 pack-years had the highest mean levels of only CRP and fibrinogen. The results of this study provide some limited evidence that GSTM1 and GSTT1 polymorphisms modify the effect of smoking on inflammation, hemostasis, and endothelial function.
近期的流行病学研究表明，谷胱甘肽 - S - 转移酶M1和T1（GSTM1/GSTT1）的基因多态性会改变吸烟对冠心病（CHD）风险的影响。由于谷胱甘肽 - S - 转移酶能够使多种有毒化合物和氧化应激产物解毒，因此GST基因分型也可能改变吸烟引发慢性炎症反应的能力。一项横断面分析利用了一个大型（n = 15,792）混血队列中的一部分参与者（n = 989），通过GST基因分型和吸烟状况的不同组合来评估炎症、止血和内皮功能的9种标志物水平。与其他基因型和吸烟的组合相比，GSTM1基因缺失（GSTM1 - 0）基因型且吸烟≥20包年的参与者，其CRP、纤维蛋白原、血管性血友病因子、ICAM - 1和VCAM - 1的平均水平最高，而白蛋白的平均水平最低。然而，GSTM1基因型与吸烟之间相互作用的正式检验仅在白蛋白方面具有统计学意义。相比之下，具有功能性GSTT1基因型（GSTT1 - 1）且吸烟≥20包年的参与者，仅CRP和纤维蛋白原的平均水平最高。本研究结果提供了一些有限的证据，表明GSTM1和GSTT1基因多态性会改变吸烟对炎症、止血和内皮功能的影响。
