CETP TaqIB、KCNE1 S38G和eNOS T-786C基因多态性与非瓣膜性心房颤动的关联研究

Study on the correlation between CETP TaqlB, KCNE1 S38G and eNOS T-786C gene polymorphisms for predisposition and non-valvular atrial fibrillation

目的研究浙江省汉族人群胆同醇酯转运蛋白基因TaqIB（CETP TaqIB）、心肌缓慢延迟整流钾离子通道（Iks）β亚单位基因S38G（KCNE1 S38G）和内皮型一氧化氮合酶基因T-786C（eNOST-786C）遗传多态性与非瓣膜性心房颤动（房颤）易感性的关联。方法选取非瓣膜性房颤患者147例，病区对照147例，采用聚合酶链反应-限制性内切酶片段长度多态性（PCR—RFLP）鉴定CETP TaqIB、KCNE1 S38G和eNOST-786C遗传多态性的基因型和等位基因分布。结果（1）CETPB1等位基因频率在非瓣膜性房颤组明显高于对照组，差异有统计学意义（OR=1．763，95％CI：1．247～2．492，P=0．002）；（2）logistic回归分析：校正性别、年龄、高血压、吸烟、BMI等混杂因素之后，CETP TaqIB基因多态性在病例组和对照组之间差异具有统计学意义；（3）多因子降维法分析表明，CETP TaqIB、KCNE1 S38G和eNOST-786C存在交互作用，3个基因多态性同时存在危险度优势比为CETP TaqIB单独存在时的1849倍。结论CETP B1等位基因是非瓣膜性房颤遗传易感性的独立危险因子。CETP B1等化基因、KCNE1 S38G等位丛因和eNOST-786C等值基因同时存在可能增加非瓣膜性房颤遗传易感性。

Objective To study whether CETP TaqIB,KCNE1 S38G and eNOS T-786C genetic polymorphisms are associated with non-valvular atrial fibrillation in the Han population from Zhejiang province. Methods Polymerase chain reaction restriction fragment length polymorphisrn assay was used to detect the distribution of alleles and genotypes of CETP TaqIB, KCNE1 S38G and eNOS T-786C in 147 patients with non-valvular atrial fibrillation and in 147 subjects as controls in Han population of Zhejiang province. Results （1） The frequency of CETP B1 allele in NVAF patients was higher than that of the control group and showing a statistically significant difference （ OR= 1. 763,95 % CI ： 1. 247-2. 492, P = 0.002）. （2） Results from logistic regression analysis revealed that： after adjustment of confounding variables such as sex, age, smoking, hypertension and body mass index, data from the binary logistic analysis showed a statistically significant difference in CETP TaqIB genetic polymorphism between patients and controls. （3） From multifactor dimensionality reduction analysis, results showed an interaction of CETP TaqIB, KCNE1 S38G and eNOS T-786C genetic polymorphisms, Odds ratio of the three simultaneously existing genetic polymorphisms was 1.849 times more than CETP TaqIB alone. Conclusion CETP BI allele was an independent risk factor for predisposition to non- valvular atrial fibrillation. These findings suggested that the simultaneous existence of CETP B1, KCNE1 S38G and eNOS T-786C allele might be elevated with the predisposition to non-valvular atrial fibrillation in the Han population of Zhejiang province.