新疆维汉民族亚甲基四氢叶酸还原酶基因多态性及血浆同型半胱氨酸与冠状动脉粥样硬化性心脏病的关系

Correlation of the polymorphism of methylene tetrahydrofolate reductase gene and plasma homocysteine with coronary heart disease in Uygur and Han ethnic groups in Xinjiang

目的:分析新疆维汉民族亚甲基四氢叶酸还原酶基因C677T多态性及其与同型半胱氨酸水平、冠状动脉粥样硬化性心脏病之间的关系,以期为冠心病的预防和优化康复治疗提供理论依据。方法:收集2004-09/2005-10在新疆医科大学第一附属医院心内科住院并行冠状动脉造影术的320例维汉民族患者,按冠状动脉造影结果分为冠状动脉粥样硬化性心脏病组(n=189)与对照组(n=131),应用聚合酶链反应-限制性内切酶长度多态性方法检测亚甲基四氢叶酸还原酶基因C677T多态性,用荧光偏振免疫分析法测定血浆同型半胱氨酸水平,并分析同型半胱氨酸及亚甲基四氢叶酸还原酶基因C677T多态性与冠心病的关联性。结果:320例全部进入结果分析。①维汉民族冠状动脉粥样硬化性心脏病组和对照组亚甲基四氢叶酸还原酶C677TCC、CT、TT3种基因型分布(维吾尔族,χ2=9.561,P=0.008;汉族,χ2=10.618,P=0.005)和等位基因频率分布(维吾尔族,χ2=4.857,P=0.028;汉族,χ2=5.158,P=0.023)差异有统计学意义;但冠状动脉粥样硬化性心脏病组和对照组内维汉不同民族基因型分布和等位基因频率分布差异无统计学意义(P>0.05)。②维汉民族冠状动脉粥样硬化性心脏病组和对照组中,亚甲基四氢叶酸还原酶C677T各基因型之间血浆同型半胱氨酸水平的差异均有统计学意义(P<0.05)。其中TT基因型的血浆同型半胱氨酸水平均高于同组同民族CT和CC型者;CT基因型与CC基因型之间血浆同型半胱氨酸水平的差异无统计学意义P>0.05)。③经多因素非条件Logistic回归分析显示,亚甲基四氢叶酸还原酶C677T基因突变(OR=1.478)、同型半胱氨酸(OR=1.057)等因素是冠状动脉粥样硬化性心脏病的危险因素。结论:①同型半胱氨酸代谢关键酶基因亚甲基四氢叶酸还原酶C677T存在多态性,无民族差异。②亚甲基四氢叶酸还原酶C677T可导致血浆同型半胱氨酸明显增高。③亚甲基四氢叶酸还原酶C677T多态性和同型半胱氨酸是新疆维汉民族冠状动脉粥样硬化性心脏病发病的独立危险因素。

AIM： To study the correlation among gone polymorphism of methylene totrahydrofolato reductaso （MTHFR） C677T gone, the level of homocysteine （Hcy） and coronary heart disease in Xinjiang Uygur and Han ethnic groups, so as to provide theoretical foundation for the prevention and rehabilitative treatment of coronary heart disease. METHODS： 320 Uygur and Han ethnic patients admitted by Department of Cardiology, the First Hospital affiliated to Xinjiang Medical University and underwent coronary arteriography between September 2004 and October 2005 ware selected and divided into coronary heart disease group （n =189） and control group （n =131） based on the results of coronary arteriography. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was applied to detect the polymorphism of MTHFR gene C677T and fluorescence polarization immunoassay was adopted to determine the plasma Hcy level, and the association of polymorphism of MTHFR and Hcy with coronary heart disease was analyzed. RESULTS： Totally 320 subjects ware involved in the result analysis. ①There ware significant differences in the genotype distribution （Uygur ethnic group x^2 =9.561, P=0.008; Han ethnic group x^2 =10.618, P=0.005） and allele frequency distribution （Uygur ethnic group x^2 =4.857, P =0.028; Han ethnic group x^2 =5.156, P =0.023） of MTHFR C677T CC, CT, TT between the coronary heart disease group and the control group. But no significance was found in the genotype distribution and allele frequency distribution between the two ethnic groups within the coronary heart disease group and control group （P 〉 0.05）. ②There were significant differences in the plasma Hcy level among different genotypes of MTHFR C677T in the coronary and control groups （P 〈 0.05）, and in Uygur and Han ethnic groups, TT genotype presented a higher plasma Hcy level compared with CT and CC in the same ethnic group and the coronary heart disease or control group, but there was no significant difference in the plasma HCY levels for CT genotype and CC genotype （P 〉 0.05）. ③Multifactor logistic regression analysis showed that MTHFR C677T gone mutation （OR =1.478） and HCY （OR =1.057） ware risk factors of coronary heart disease. CONCLUSION： ①There is polymorphism in Hcy metabolic key enzyme gene MTHFR C677T, and no difference is found between ethnic groups. ②The gone mutation of MTHFR C677T can increase the plasma Hcy level markedly. ③The polymorphism of MTHFR C677T and HCY are the independent risk factors of coronary heart disease in Xinjiang Uygur and Han ethnic groups.