miRNA基因多态性与早发冠心病的遗传易感性研究

Genetic susceptibility association study on polymorphisms of miRNAs genes and the risk of premature coronary artery disease

目的:通过病例对照研究,探讨江苏省南京地区汉族人群hsa-miR-196a2rs11614913T→C,hsa-miR-499rs3746444T→C单核苷酸多态性改变与早发冠心病(pCAD)发生风险的关系。方法:采用序贯设计收集冠状动脉造影确诊的pCAD病例233例和非冠心病对照者349例。用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)检测hsa-miR-196a2rs11614913T→C和hsa-miR-499rs3746444T→C多态性改变基因型,比较变异基因型与pCAD发生的关系。结果:rs3746444T→C多态性改变中,与TT基因型相比,CC基因型的个体罹患pCAD的风险增加123%(校正OR=2.23,95%CI:1.09～4.57);以对照组TG、TC、HDL-C和LDL-C水平中位数为界值分组,高于对照组HDL-C中位数(>1.11mmol/L)水平个体较低HDL-C者患冠心病的风险显著降低(校正OR=0.46,95%CI:0.29～0.74)。分层分析未发现两位点多态性改变与高血脂水平在pCAD发生中存在交互作用。结论:hsa-miR-499rs3746444T→C多态性改变可增加pCAD的发病风险。

Objective：To investigate the associations between the hsa-miR-196a2 rs11614913 T→C and hsa-miR-499 rs3746444 T→C polymorphisms and the risk of pCAD in nan jing han population of jiangsu province. Method：The 233 pACD patients diagnosed by CAG and 349 with controls gender and age frequency matched pCAD-free were enrolled from Zhongda Hospital.The genotypes of hsa-miR-196a2 rs11614913 T→C and hsa-miR-499 rs3746444 T→C polymorphisms were detected by PCR-RFLP in case-control study to evaluate the association between the variant genotypes and the risk of pACD. Result：Compared with the wide genotype TT,subjects with the variant genotypes CC of rs3746444 T→C was associated with a 123% increased risk of pCAD（adjusted OR=2.23,95%CI： 1.09-4.57）.When the control median serum HDL-C levels（1.11 mmol/L） were considered as the cutoff value,subjects with higher HDL-C levels was associated with a 54% decreased risk of pCAD（adjusted OR=0.46,95%CI： 0.29-0.74）.Stratified analyses did not show interaction existed between the risk effect of CT/TT genotypes and high blood lipid levels in pathogenesis of pCAD. Conclusion：The polymorphism of hsa-miR-499 rs3746444 T→C is associated with the increased risk of pCAD.