Fumeron Frédéric, Betoulle Dina, Nicaud Viviane, Evans Alun, Kee Frank, Ruidavets Jean-Bernard, Arveiler Dominique, Luc Gérald, Cambien François
EA 3516, Faculté de Médecine Xavier Bichat, Paris, France.
Circulation. 2002 Jun 25;105(25):2943-5. doi: 10.1161/01.cir.0000022603.92986.99.
Depression is a risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors reduce this risk. The site of action is the serotonin transporter (SLC6A4), which is expressed in brain and blood cells. A functional polymorphism in the promoter region of the SLC6A4 gene has been described. This polymorphism may be associated with the risk of MI.
The SLC6A4 polymorphism has been investigated by polymerase chain reaction in 671 male patients with MI and in 688 controls from the Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM) multicentric study. Percentages for LL, LS, and SS genotypes were 35.5%, 45.4%, and 19.1%, respectively, for cases versus 28.1%, 49.1%, and 22.8%, respectively, for controls. S allele frequency was 41.8% and 47.4% for cases and controls, respectively. After adjustment for age and center by using multivariable logistic regression, the odds ratio for MI associated with the LL genotype was 1.40 (95% CI 1.11 to 1.76, P=0.0047).
The LL genotype of the SLC6A4 polymorphism is associated with a higher risk of MI. This could be attributable to the effect of the polymorphism on serotonin-mediated platelet activation or smooth muscle cell proliferation or on other risk factors, such as depression or response to stress.
抑郁症是心肌梗死(MI)的一个风险因素。选择性5-羟色胺再摄取抑制剂可降低此风险。作用部位是5-羟色胺转运体(SLC6A4),其在脑细胞和血细胞中表达。已描述了SLC6A4基因启动子区域的一个功能性多态性。这种多态性可能与MI风险相关。
通过聚合酶链反应对来自心肌梗死病例对照研究(ECTIM)多中心研究的671例男性MI患者和688例对照进行了SLC6A4多态性研究。病例组中LL、LS和SS基因型的百分比分别为35.5%、45.4%和19.1%,而对照组分别为28.1%、49.1%和22.8%。病例组和对照组的S等位基因频率分别为41.8%和47.4%。使用多变量逻辑回归对年龄和中心进行校正后,与LL基因型相关的MI比值比为1.40(95%CI 1.11至1.76,P = 0.0047)。
SLC6A4多态性的LL基因型与较高的MI风险相关。这可能归因于该多态性对5-羟色胺介导的血小板活化或平滑肌细胞增殖的影响,或对其他风险因素的影响,如抑郁症或应激反应。