新疆维汉民族胱硫醚-β-合成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

Polymorphism of cystathionine-beta-synthetase gene and plasma homocysteine in relation to coronary heart disease in Uygur and Han populations in Xinjiang

目的:分析新疆维汉民族胱硫醚-β-合成酶基因T833C多态性及其与同型半胱氨酸水平、冠状动脉粥样硬性心病之间的关系,探讨胱硫醚-β-合成酶基因T833C基因突变是否增加维汉民族冠状动脉粥样硬化性心脏病的危险。方法:选择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189例与对照组131例。冠状动脉粥样硬化性心脏病组冠状动脉造影显示,左冠状动脉主干、左前降支、左回旋支或右冠状动脉中至少1支血管狭窄程度≥50%,维吾尔族75例,汉族114例,(56.0±10.5)岁。对照组冠状动脉造影未发现任何可辨认的斑块和狭窄,维吾尔族48例,汉族83例,(53.6±10.8)岁。纳入对象对实验目的均知情同意。应用扩增阻滞突变体系方法分析胱硫醚-β-合成酶基因T833C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胱硫醚-β-合成酶基因T833C多态性与冠状动脉粥样硬化性心脏病的关联性。结果:320例患者全部进入结果分析。①维汉民族冠状动脉粥样硬化性心脏病组和对照组胱硫醚-β-合成酶基因T833CTT,TC,CC三种基因型分布和等位基因频率分布,以及组内维汉不同民族基因型分布和等位基因频率分布差异均无统计学意义。②维汉民族冠状动脉粥样硬化性心脏病组和对照组中,CC基因型的血浆同型半胱氨酸水平高于同组同民族TC和TT型者[对照组:汉族:(15.52±6.77),(11.01±5.00),(11.05±6.13)μmol/L,维吾尔族:(14.59±5.24),(11.05±1.92),(9.76±3.20)μmol/L;冠状动脉粥样硬化性心脏病组:汉族:(22.92±17.84),(16.06±8.27),(14.67±8.92)μmol/L,维吾尔族:(17.77±8.61),(12.82±6.34),(12.21±5.60)μmol/L,P<0.05];TC和TT基因型之间血浆同型半胱氨酸水平的差异不显著。结论:①同型半胱氨酸代谢关键酶基因胱硫醚-β-合成酶基因T833C存在多态性,维汉民族间略有差异,但不显著。②胱硫醚-β-合成酶基因T833C基因突变可导致血浆同型半胱氨酸明显增高。③胱硫醚-β-合成酶基因T833C基因多态性与新疆维汉民族冠状动脉粥样硬化性心脏病发病无相关性。

AIM： To study the correlation among gene polymorphism of cystathionine-β-synthetase （CBS） T833C gene, the level of homocysteine （Hcy） and coronary heart disease （CHD） in Xinjiang Uygur and Han populations, and find out whether the base mutation of CBS T833C gene will increase CHD risk in the Uygur and Han population. METHODS： 320 Uygur and Han patients who ware admitted by Cardiology Department of the First Hospital affiliated to Xinjiang Medical University and underwent coronary arteriography between September 2004 and October 2005 were enrolled, and divided into CHD group （n =189） and control group （n =131） based on the results of coronary arteriography. The results of the CHD group showed that the stenosis was found ≥50% in at least one of left coronary artery main stem, left anterior descending branch, left circumflex artery or auricular artery of left ventricle of 75 cases of Uygur and 114 Hans aged （56.0±10.5） years. The results of the control group did not show any plaque or stenosis in 48 Uygur and 83 Han aged （53.6±10.8） years. All the patients ware informed and agreed to participate in. Amplification refractory mutation system （ARMS） was applied to analyze the polymorphism of CBS gene T833C and fluorescence polarization immunoassay was applied to determine the plasma Hcy level, and the association of polymorphism of CBS gene and plasma Hcy with CHD was analyzed. RESULTS： Totally 320 persons were involved in the result analysis. ①There was no statistical significance in the difference of the genotype distribution and allele frequency distribution of CBS T833C TT, TC and CC between CHD group and the control group in Uygur and Han ethnic groups, so was in the difference of the genotype distribution and allele frequency distribution between the two ethnic groups within CHD group and the control group. ②The plasma Hcy level of CC genotype in the two groups was higher than that of TC and TT ones in the same ethnic group and CHD or control group [control group： Han： （15.52±6.77）, （11.01±5.00）, （11.05±6.13） μmol/L; Uygur： （14.59±5.24）, （11.05±1.92）, （9.76±3.20） μmol/L; CHD group： Han： （22.92±17.84）, （16.06±8.27）, （14.67±8.92） μmol/L; Uygur： （17.77±8.61）, （12.82± 6.34）, （12.21 ±5.60） μmol/L, P 〈 0.05], but there was no significant difference in the plasma Hcy levels for TC genotype and TT genotype. CONCLUSION： ①There is polymorphism between Hcy metabolic key enzyme gene CBST833C. There are some differences between the two ethnic groups but the difference has no statistical significance. ②The gene mutation of CBST833C can increase the plasma Hcy level markedly.③The polymorphism of CBS T833C gene is not related to CHD occurrence in Xinjiang Uygur andHan ethnic groups.