冠心病患者胸腺苷合成酶多态性的探讨

目的研究胸腺苷合成酶(TS)5’-非翻译区(UTR)28bp串联重复序列多态性、3-’UTR1494bp位6bp插入或缺失多态性与血浆同型半胱氨酸(Hcy)水平及冠心病之间的关系。方法用多聚酶链式反应(PCR)方法检测122例冠心病患者(冠状动脉造影显示至少有一支血管狭窄≥50%)与56例对照组(冠状动脉造影未发现任何可辨认斑块或狭窄)的TS 5-’UTR 28bp串联重复序列多态性;用聚合酶链反应-限制性片段多态性(PCR-RFLP)分析3-’UTR1494bp位6bp插入或缺失多态性;用荧光衍生后高压液相色谱分离法检测血浆总Hcy水平。结果(1)冠心病组的血浆Hcy水平(12.99±4.76)μmol/L高于对照组(10.95±4.75)μmol/L(P=0.009)。(2)TS5-’UTR 28bp串联重复序列有三种基因型(3R/3R,3R/2R,2R/2R),这三种基因型频率在冠心病组和对照组之间的分布有差异(P=0.029);TS28各基因型个体的Hcy水平在冠心病组高于对照组(P=0.03)。3R/3R、3R/2R基因型个体的Hcy水平均高于2R/2R型个体(分别为P<0.001和P=0.011),但3R/3R基因型个体与3R/2R基因型个体的Hcy水平间的差异没有统计学意义(P=0.979)。(3)TS3-’UTR6bp插入或缺失多态性有三种基因型(+6bp/+6bp,+6bp/-6bp,-6bp/-6bp),这三种基因型频率在冠心病组和对照组之间的分布差异无显著性(P>0.05)。TS6各基因型个体的Hcy水平在冠心病组高于对照组(P=0.006)。冠心病组TS6 bp各基因型个体间Hcy水平的的差异均没有统计学意义(P均>0.05)。结论(1)高Hcy血症与冠心病有关系。(2)TS基因5-’UTR28bp串联重复序列多态性可能是冠心病发病中的一个遗传因素。3 R与冠心病组个体的Hcy水平有关系。

Polymorphisms of thymidylate synthase in patients with coronary heart disease

Objective To study the relationship between polymorphism of 28bp tandem repeat sequence in 5'-UTR and 6-bp variation at bp1494 in the 3'-UTR of thymidylate synthase(TS),plasma homocysteine(Hcy) levels and coronary heart disease.Methods All the subjects were underwent coronary angiography.Subjects(n=122) with≥50% stenosis in at least one coronary vessels were defined as CHD.Subjects(n=56) without any stenosis in all coronary vessels were defined as controls.TS 28bp genotyping was analyzed using PCR and TS 6bp genotyping was performed using PCR-RFLP.Total plasma Hcy levels were measured by HPLC with fluorescence detection.Results(1)Mean Hcy concentration was significantly higher in CHD patients(12.99±4.76μmol/L)than that in controls(10.95±4.75μmol/L)(P=0.009).(2)There was significant difference in TS 28bp genotype frequencies between CHD group and controls respectively(P=(0.029)),Hcy levels of different TS28 genetypes in the CHD group were higher than that in controls(P=0.03).In the CHD group,Hcy levels of 3R/3R were higher than that of 2R/2R(P<0.001) and Hcy levels of 3R/2R was higher than that of 2R/2R(P=0.011).There was no difference of the Hcy levels between 3R/3R and 3R/2R(P=0.979).(3)No significant difference in TS 6bp genotype frequencies between the two groups was observed(P=0.285).Hcy levels of different TS6 genetypes in the CHD group were higher than that in controls(P=0.006).In CHD group,there was no significant difference between the Hcy levels in the individuals with the genetypes of +6bp/+6bp,+6bp/-6bp,(-6bp)/-6bp.Conclusion(1)Hyperhomocysteinemia is associated with CHD.(2)Polymorphism of TS 5'-UTR 28 bp correlates with CHD and it may be a possibly genetics factor of CHD.