冠心病患者胸腺苷合成酶多态性的探讨

Polymorphisms of thymidylate synthase in patients with coronary heart disease

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。

Objective To study the relationship between polynaorphisa-n of 28bp tandena repeat sequence in 5＇-UTR and 6- bp variation at bp1494 in the 3＇-UTR of thymidylate synthase（TS）, plasma homcysteine （Hey） levels and coronary heart disease. Methods All the subjects were underwent coronary angiography. Subjects （ n=121） 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 Hey levels were measured by HPLC with fluorescence detection. Results （ 1 ） Mean Hey concentration was significantly higher in ClAD patients （ 12.99 ± 4.76μmol/L） than that in controls（ 10.95 ± 4.75μmol/L） （ P = 0. 009 ）. （2） There was signlfieant difference in TS 28bp genotype frequencies between CHD group and controls respectively（ P = 0.029）, Hey levels of different T828 genetypes in the CHD group were higher than that in controls （P=0.03）. In the CHD group, Hey levels of 3R/3R were higher than that of 2R/2R（ P〈0. 001 ） and Hey levels of 3R/2R was higher than that of 2R/2R（P=0.011）. There was no difference of the Hey levels between 3R/3R and 3R/2R（ P =0.979）. （3）No significant difference in TS 6bp genotype frequencies between the two groups was boserved （ P = 0. 285 ）. Hey 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 Hey levels in the individuals with the genetypes of ＋ 6bp/＋ 6bp, ＋ 6bp/- 6bp, -6bp/-6bp. Conclusion （1 ）Hyperhomocysteinenaia 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.