5-羟色胺转运体基因启动子连锁多态区多态性与早发心肌梗死及血小板膜糖蛋白Ⅰb的关系

Association of serotonin transporter gene linked polymorphic region polymorphism with early onset myocardial infarction and platelet membrane glycoprotein Ⅰ b

目的研究中国北方汉族人群5-羟色胺转运体基因启动子连锁多态区（5-hydroxytryptamine transporter gene linked polymorphic region，5-HTTLPR）缺失／插入多态性与早发心肌梗死及血小板膜糖蛋白Ⅰb（glycoprotein Ⅰb，GPIb）的关系。方法采用性别、年龄配对方法，选择150例早发心肌梗死患者和150例冠状动脉造影阴性对照者作为研究对象，采用聚合酶链反应技术检测受试对象5-HTTLPR多态性位点的基因型和等位基因分布，全血流式细胞术检测血小板膜GPIb阳性百分率及平均荧光强度。结果5-HTTLPR基因型LL型、LS型和SS型在心肌梗死组分布频率分别为32％，47％，21％，在对照组为17％，43％和39％（P〈0．01）。L等位基因频率在心肌梗死组明显高于对照组（56％vs39％，P％0．01）。心肌梗死组和对照组内不同基因型的血小板膜GPIb指标比较，LL基因型的血小板膜GPIb阳性百分率及荧光强度均低于同组LS型和SS型（均P〈0．01），多因素Logistic回归分析结果提示5-HTTLPR的LL基因型与早发心肌梗死发病独立相关（OR=1．961，P=0．037）。结论5-HTTLPR的LL纯合子血小板活化程度增高，LL基因型可能与中国北方汉族人群早发心肌梗死的发病相关联。

Objective To investigate the association of serotonin transporter gene linked polymorphic region （5-HTTLPR） insertion/deletion polymorphism with early onset myocardial infarction（MI） and platelet membrane glycoprotein Ⅰ b（GP Ⅰ b） in Northern Han population of China. Methods A total of 150 patients with early onset MI and 150 age- and sex-matched controls with negative coronary arteriography were genotyped for the 5-HTTLPR polymorphism by using a polymerase chain reaction-based technique. The percentage of positive platelet membrane GP I b and the average fluorescence intensity were quantified by flow cytometry. Results The genotype frequencies of LL, LS and SS in the 5-HTTLPR were 32%, 47% and 21% in the MI patients, 17%, 43% and 39% in the controls respectively（P〈0.01）. The L allele frequency in the MI patients was significantly higher than that of the control group （56 % vs 39 %, P〈0.01）. The percentage of positive platelet membrane GP I b and the fluorescence intensity in subjects with LL homozygote were markedly lower than that of LS and SS genotypes in the MI and control groups （all P〈0. 01）. Multivariate logistic regression analysis showed that the 5-HTTLPR LL genotype was independently related to the occurrence of early onset MI（OR= 1. 961, P= 0. 037）. Conclusion The LL genotype of the 5-HTTLPR might be associated with the susceptibility to developing early MI in Northern Han population of China. The platelet activation is increased in individuals of LL genotype.