亚甲基四氢叶酸还原酶基因C667T多态性与冠状动脉慢血流现象的关系研究

Association of MTHFR polymorphisms with risk of coronary slow flow phenomenon

目的观察亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与中国南方汉族人群中冠状动脉慢血流现象(CSFP)的关系,进一步探讨遗传因素在CSFP发病中的意义。方法收集经冠状动脉血管造影证实冠脉正常的患者214例作为研究对象,并利用校正的TIMI帧数法(CTFC)分组为慢血流组(143例)和对照组(71例),应用焦磷酸测序法(Pyrosequencing)检测患者C677T基因表型,分析MTHFR基因C677T多态性与CSFP的关系。结果慢血流组MTHFR基因(TT+TC)基因型和T等位基频率均明显高于对照组(69.2%、49.3%。x^2=8.05,P<0.01;4217%、296%,x^2=6.87,P<0.01)。慢血流组男性比例明显高于对照组(59.4%、36.6%,x^2=9.90,P<0.01),同型半胱氨酸(Hcy)和尿酸(UA)水平明显高于对照组(P<0.05或0.01),慢血流组叶酸(FA)和高密度脂蛋白胆固醇(HDL-C)水平明显低于对照组(P<0.05),Logistic回归分析均显示(TT+TC)基因型[OR=1.962,95%CI(1.049~3.669),P<0.05]、Hcy水平升高[OR=1.087,95%CI(1.012-1.168),P<0.05]、男性[OR=2.507,95%CI(1.347~4.664),P<0.01]和UA水平升高[OR=1.008,95%CI(1.003~1.013),P<0.01]患者CSFP发病风险增加。结论MTHFR基因C677T多态性与CSFP发病相关,携带下等位基因可能是中国南方汉族人群冠状动脉慢血流现象发病的危险因素之一。

Objective To investigate the association of methylenetetrahydrofolate reductase （MTHFR） C677T polymorphisms with risk of coronary slow flow phenomenon （CSFP）. Methods One hundred and forty three patients with CSFP and 71 controls were included in this study. CSFP were diagnosed by the corrected TIMI frame count method. The polymorphisms of MTHFR C677T were determined by pyrosequencing in two groups. Results The TT and TC genotype frequency, and T allele frequency in CSFP patients were higher than those in the controls （69.2%, 49.3%, Х^2=8.05, P〈0.01; 42.7%, 29.6%, Х^2=6.87, P〈 0.01）. Male to female ratio was higher in CSFP group （59.4%, 36.6%, Х^2= 9.90, P〈0.01） than in controls. Serum homoeysteine （Hey） and uric acid （UA） levels were higher, folic acid and high-density lipoprotein cholesterol levels were lower in CSFP patients than those in controls （P〈0.05 and 0.01）. After other risk factors were adjusted, TT and TC genotype （OR=1.962, 95%CI 1.049 N 3.669, P〈0.05）, Hcy （OR=1.087, 95%CI 1.012 - 1.168, P〈0.05）, male sex （OR=2.507, 95%CI 1.347 - 4.664, P〈0.01） and UA （OR=1.008, 95%CI 1.003 - 1.013, P〈0.01） were independent risk factors for CSFP. Conclusion The high frequency of allele T in MTHER gene C677T may be a risk factor for CSFP in the southern Chinese population.