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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 relationship between C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and coronary artery slow flow phenomenon (CSFP) in Han population of southern China, and to explore the significance of genetic factors in the pathogenesis of CSFP. Methods Totally 214 patients with normal coronary artery confirmed by coronary angiography were enrolled. The patients were divided into slow blood flow group (n = 143) and control group (n = 71) by using corrected TIMI frame number method (CTFC) The C677T gene phenotype was detected by Pyrosequencing and the relationship between MTHFR gene C677T polymorphism and CSFP was analyzed. Results The frequencies of TT + TC genotype and T allele in slow blood flow group were significantly higher than those in control group (69.2%, 49.3% .x ~ 2 = 8.05, P <0.01; 4217%, 296%, x ~ 2 = 6.87, P <0.01). The proportion of male in slow blood flow group was significantly higher than that in control group (59.4%, 36.6%, x 2 = 9.90, P <0.01), and the levels of homocysteine (Hcy) and uric acid (P <0.05 or 0.01). The levels of FA and HDL-C in the slow blood flow group were significantly lower than those in the control group (P <0.05). Logistic regression analysis showed that the genotypes of TT + TC [ OR = 1.962, 95% CI 1.049-3.669, P <0.05], Hcy increased [OR = 1.087,95% CI 1.012-1.168, P 0.05] (1.347 ~ 4.664), P <0.01] and the level of UA increased [OR = 1.008,95% CI (1.003 ~ 1.013), P <0.01]. Conclusions The C677T polymorphism of MTHFR gene is associated with the pathogenesis of CSFP. The lower allele may be one of the risk factors of coronary blood flow in South Han Chinese population.