Goldenberg Ilan, Moss Arthur J, Block Robert, Ryan Daniel, Corsetti James P, McNitt Scott, Eberly Shirley W, Zareba Wojciech
Cardiology Units of the Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Ann Noninvasive Electrocardiol. 2007 Oct;12(4):364-74. doi: 10.1111/j.1542-474X.2007.00186.x.
Cigarette smoking and the common B1 allele of the TaqIB polymorphism have both been reported to be associated with increased cholesteryl ester transfer protein (CETP) activity and altered lipoprotein levels. Thus, it is possible that the combined presence of these two respective environmental and genetic factors may enhance cardiovascular risk. We hypothesized that susceptibility to early onset myocardial infarction (MI) among cigarette smokers may be related to the presence of TaqIB polymorphism in the CETP gene.
The age at onset of a first MI among current (n = 199), past (n = 345), and never (n = 270) smokers was related to the presence of the TaqIB1 and B2 alleles in a cohort of 814 first MI patients.
Multivariate regression analysis demonstrated that cigarette smoking was associated with a significant increase in the risk for early onset MI only among carriers of the TaqIB1 allele: current smokers with the B1B1 and B1B2 genotypes displayed a respective 9.4 (P < 0.001) and 8.4 (P < 0.001) year reduction in the age at onset of a first MI compared with never smokers, and past smokers with these genotypes exhibited a respective 3.8 (P = 0.003) and 3.7 (P = 0.01) year reduction. By contrast, current and past smoking was not associated with a significant increase in the risk for early onset MI among B2B2 homozygotes (3.0 [P = 0.28] and 0.2 [P = 0.93] year reduction, respectively). The smoking x genotype interaction was statistically significant (P = 0.04).
The current findings suggest that genetic factors may modify susceptibility to early onset MI among cigarette smokers.
据报道,吸烟和TaqIB多态性的常见B1等位基因均与胆固醇酯转运蛋白(CETP)活性增加及脂蛋白水平改变有关。因此,这两种各自独立的环境和遗传因素共同存在可能会增加心血管疾病风险。我们推测,吸烟者中早发性心肌梗死(MI)的易感性可能与CETP基因中TaqIB多态性的存在有关。
在814例首次发生MI的患者队列中,将当前吸烟者(n = 199)、既往吸烟者(n = 345)和从不吸烟者(n = 270)首次发生MI的发病年龄与TaqIB1和B2等位基因的存在情况进行关联分析。
多变量回归分析表明,仅在TaqIB1等位基因携带者中,吸烟与早发性MI风险显著增加有关:与从不吸烟者相比,B1B1和B1B2基因型的当前吸烟者首次发生MI的发病年龄分别提前了9.4岁(P < 0.001)和8.4岁(P < 0.001),具有这些基因型的既往吸烟者发病年龄分别提前了3.8岁(P = 0.003)和3.7岁(P = 0.01)。相比之下,在B2B2纯合子中,当前和既往吸烟与早发性MI风险的显著增加无关(分别提前3.0岁[P = 0.28]和0.2岁[P = 0.93])。吸烟与基因型的交互作用具有统计学意义(P = 0.04)。
目前的研究结果表明,遗传因素可能会改变吸烟者中早发性MI的易感性。