摘要目的 通过病例对照研究设计,探讨江苏省南京地区汉族人群hsa-微小RNA-1( hsa-miRNA-1)靶基因COG6 rs9548934C→T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pCAD病例226例和非冠心病对照275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-miRNA-1靶基因COG6 rs9548934C→T各基因型,比较变异基因型与pCAD发生的关系.结果 在rs9548934C→T多态性改变中,与CC基因型相比,携带CT,CT/TT基因型的个体罹患冠心病的风险分别降低45％和36％(校正OR=0.55,95％ CI=0.36 ～0.82,P=0.003；校正OR=0.64,95％CI=0.44～0.92,P=0.015)；以对照组血脂水平中位数为界值,高甘油三酯(TG)水平的个体较低TG者患冠心病的风险增高1.32倍(校正OR=2.32,95％ CI=1.57 ～ 3.41,P＜0.001)；高高密度脂蛋白胆固醇(HDL-C)水平个体较低HDL-C者患冠心病的风险显著降低(校正OR =0.48, 95％ CI =0.31～0.75,P=0.001).分层分析提示,携带CT/TT基因型个体较CC携带者罹患冠心病的风险在女性中降低更为显著(校正OR=0.54,95％CI=0.30 ～0.97,P=0.040)；携带CT/TT基因型个体罹患冠心病的风险在低血清TG、总胆固醇(TC)、HDL-C、低密度脂蛋白胆固醇(LDL-C)水平人群中降低更为显著(校正OR =0.62,95％CI=0.39～0.98,P =0.040;校正OR =0.55,95％CI=0.35～0.85,P=0.008；校正OR =0.43,95％ CI=0.22～0.87,P=0.018;校正OR =0.49,95％CI=0.32～0.75,P=0.001).结论 hsa-miRNA-1靶基因COG6 rs9548934C→T多态性改变与pCAD的发病风险降低相关,尤其在女性和低血脂水平的人群中保护作用更为显著.

abstractsObjective To investigate the association between the genetic variant of miRNA-1 target gene COG6 rs9548934 C→T and the risk of premature coronary artery disease (pCAD).Methods This study included 226 pACD patients and 275 gender and age matched pCAD-free controls hospitalized in our hospital,diagnosis was made based on coronary angiography ( CAG ) results.The genotypes of miRNA-1 target gene COG6 rs9548934 C→T were detected by PCR-RFLP.Results Compared with the wide genotype CC,subjects with the variant genotypes CT of rs9548934 C→T was associated with a 45％ lower risk of pACD (adjusted OR =0.55,95％ CI =0.36 -0.82,P =0.003),and the subjects with CT/TT genotypes were also associated with a significantly lower risk of pACD ( adjusted OR =0.64,95％ CI =0.44 - 0.92,P=0.015).Using the median serum TG level (1.20 mmol/L) in control group as the cutoff value,subjects with higher serum TG levels were associated with increased risk of pACD after adjustment for age,gender and BMI ( adjusted OR =2.32,95％ CI =1.57 - 3.41,P ＜ 0.001 ).In addition,subjects with higher HDL-C levels were associated with significantly lower risk of pACD ( adjusted OR =0.48,95％ CI =0.31 -0.75,P =0.001 ).Stratified analyses showed that the risk reduction for pCAD in CT/TT genotypes carriers was more significant in the female subjects ( adjusted OR =0.54,95％ CI =0.30 - 0.97,P=0.040),and in subjects with lower TG,TC,HDL-C and LDL-C levels (adjusted OR =0.62,95％ CI =0.39 - 0.98,P =0.040; adjusted OR =0.55,95 ％ CI =0.35 - 0.85,P =0.008; adjusted OR =0.43,95％CI=0.22-0.87,P=0.018; adjusted OR=0.49,95％CI=0.32-0.75,P=0.001,respectively).Conclusion The polymorphism of miRNA-1 target gene COG6 rs9548934C→T is associated with lower risk of pCAD,especially in female subjects and subjects with lower serum lipid levels.