Yang Xu, Gao Yan, Zhou Jin, Zhen Yisong, Yang Yuejin, Wang Jizheng, Song Li, Liu Yuqing, Xu Haiyan, Chen Zaijia, Hui Rutai
Sino-German Laboratory for Molecular Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, PR China.
Clin Chim Acta. 2006 Feb;364(1-2):230-4. doi: 10.1016/j.cccn.2005.07.007. Epub 2005 Aug 18.
Homocysteine thiolactone adducts have been proposed as the culprit of homocysteine related cardiovascular diseases. We studied the association of these adducts in plasma, and the gene polymorphism of paraoxonase-2 with coronary heart disease.
254 patients and 308 controls were recruited for the study. Homocysteine thiolactone adducts were determined with ELISA. The codon 311 polymorphism of paraoxonase-2 gene was genotyped by using polymerase chain reaction and restrictive digestion.
The plasma level of homocysteine thiolactone adducts were significantly higher in patients than in controls (40.65 +/- 10.87 u/ml vs. 30.58 +/- 10.20 u/ml, P <0.01), with odds ratio of 7.34 (95% confidence interval 4.020-13.406, P <0.01), and increased according to the number of atherosclerotic coronary arteries: 35.59 +/- 10.34 units/ml (n = 76); 41.88 +/- 8.83 (n = 70) and 43.13 +/- 11.47 (n = 108) in subjects with 1, 2 and 3 affected arteries, respectively (r =0.174, P < 0.01). The frequency of CC genotype was significantly higher in patients with coronary heart disease (7.48%) than in controls (1.62%, P < 0.01), with adjusted odds ratio of 4.367 (95% confidence interval: 1.178 to 16.191, P < 0.01), so was the C allele (23.2% vs. 14.9%, P < 0.05).
High plasma homocysteine thiolactone adducts and the CC 311 genotype of paraoxonase-2 gene may be the emerging risk factor for coronary heart disease.
同型半胱氨酸硫内酯加合物被认为是同型半胱氨酸相关心血管疾病的罪魁祸首。我们研究了血浆中这些加合物以及对氧磷酶-2基因多态性与冠心病的关联。
招募了254例患者和308名对照进行研究。采用酶联免疫吸附测定法测定同型半胱氨酸硫内酯加合物。使用聚合酶链反应和限制性酶切对血清对氧磷酶-2基因的311密码子多态性进行基因分型。
患者血浆中同型半胱氨酸硫内酯加合物水平显著高于对照组(40.65±10.87单位/毫升对30.58±10.20单位/毫升,P<0.01),比值比为7.34(95%置信区间4.020 - 13.406,P<0.01),并且根据动脉粥样硬化冠状动脉的数量增加:在1支、2支和3支受影响动脉的受试者中分别为35.59±10.34单位/毫升(n = 76);41.88±8.83(n = 70)和43.13±11.47(n = 108)(r = 0.174,P<0.01)。冠心病患者中CC基因型频率显著高于对照组(7.48%对1.62%,P<0.01),校正比值比为4.367(95%置信区间:1.178至16.191,P<0.01),C等位基因也是如此(23.2%对14.9%,P<0.05)。
高血浆同型半胱氨酸硫内酯加合物和对氧磷酶-2基因的CC 311基因型可能是冠心病新出现的危险因素。