微小RNA-1靶基因多态性与早发冠心病发生风险的关联研究

Association study on the microRNA-1 target gene polymorphism and the risk of premature coronary artery disease

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COG6rs9548934C→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。用聚合酶链反应一限制性片段长度多态性方法（PCR—RFLP）检测hsa—miRNA-1靶基因COG6rs9548934C→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／啊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％C／=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c｜r／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％C／=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COG6rs9548934C→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。

Objective To investigate the association between the genetic variant of miRNA-1 target gene COC,6 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 COC,6 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% C1 = 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.