细胞间黏附分子-1基因K469E多态性与冠状动脉支架置入后再狭窄相关性的初步探讨

A preliminary study of association between the polymorphism K469E of intercellular adhesion molecule-1 gene and restenosis after coronary stenting

目的 炎症反应是冠状动脉支架置入后再狭窄的重要因素 ,细胞间黏附分子 1(ICAM 1)是介导白细胞在血管内皮细胞表面紧密黏附的重要黏附分子。本研究的目的在于探索ICAM 1基因多态性与中国北方汉族人群中冠状动脉支架置入后再狭窄的相关性。方法 收集冠状动脉支架术后行冠状动脉造影随访的患者 12 4例 ,同时收集传统危险因素、手术相关因素信息。应用PCR RFLP方法确定ICAM 1K4 6 9E基因型。结果 入选的 12 4例患者中再狭窄者 72例 ,无再狭窄者 5 2例 ;12 4例中ICAM 1K4 6 9E基因型频率为 :KK纯合子 5 0 8% ,EE纯合子 7 3% ,EK杂合子 4 1 9%。再狭窄患者中KK纯合子和E等位基因携带基因型的频率分别为 5 8 3%、4 1 7% ;无再狭窄患者中二者的频率分别为 4 0 4 %、5 9 6 %。二者分布差异有显著性 (P =0 0 4 9)。调整混杂因素后显著性差异更为明显 ,KK纯合子OR值为 2 6 ,95 %可信区间为 1 2～ 5 8(P =0 0 18)。危险因素分层发现在肥胖 (体重指数≥ 2 7)、高脂血症患者KK纯合子的再狭窄危险更高 ,OR值分别为 9 3、3 7(P值均小于 0 0 5 )。结论 ICAM 14 6 9KK纯合子冠状动脉支架置入后再狭窄危险性较高 ,且在肥胖或高脂血症患者中作用更为显著。

Objective Inflammation is a major cause of restenosis after coronary stenting. Intercellular adhesion molecule-1 (ICAM-1) is an important member of adhesion molecule that plays a key role in the tight adhesion between leukocyte and vascular endothelium. The main target of this research is to examine the relationship between the polymorphism of ICAM-1 gene and restenosis after coronary stenting in north Chinese population. Methods One hundred and twenty four cases were enrolled who underwent coronary stenting and coronary angiography at least 3 months after the procedure. The information of clinical risk factors and procedure-related factors was collected. Genome DNA was collected from venous blood. The production of polymerase chain reaction(PCR) was digested with the restriction enzyme BstU I, separated in agarose gel, and visualized by ultra-violet light. The genotype was judged by the location of the band. Results In total 124 enrolled patients, 72 cases developed in-stent restenosis, and the others were free from restenosis. The frequency of three genotypes of ICAM-1 K469E polymorphism was: KK 50.8%, EE 7.3%, EK 41.9%. In the coronary angiography follow-up cases, the frequency of KK genotype and E allele carriers in the patients with restenosis were 58.3%, 41.7% respectively. And that in the patients without restenosis were 40.4%, 59.6% respectively. The distribution of these two genotypes between with and without restenosis patients was significantly different ( P =0.049). In multivariate logistic regression, the difference between two groups was more appare- nt. The odds ratio of KK homozygotes vs E allele carriers was 2.6, 95% CI 1.2-5.8 ( P =0.018). After graded with risk factors, it was found that KK genotype was a stronger predictor of in-stent restenosis in obesity or hyperlipemia patients, and the OR was 9.3?3.7 respectively( P <0.05). Conclusion KK homozygotes of ICAM-1 codon 469 may have a higher risk of restenosis after coronary stenting, especially in obesity or hyperlipemia patients.