间隙性连接蛋白37基因1019C／T多态性与经皮冠状动脉介入术后支架内再狭窄的相关性研究

Association between 1019C/T polymorphism of Connexin 37 gene and restenosis after coronary stenting

目的评估无锡地区人群间隙性连接蛋白37（Connexin37，CX37）基因1019C／T多态性与经皮冠状动脉介人术（percutaneous coronary intervention, PCI）术后支架内再狭窄的相关性。方法532例PCI术后在我院复查冠脉造影的冠心病患者，按造影结果分为支架内再狭窄组（67例）和无支架内再狭窄组（465例），501名健康人群作为正常对照组，均采用基因测序技术对CX37基因1019C／T多态性位点基因型进行检测，比较3组人群中基因型及等位基因分布差异。结果（1）在冠心病组与正常对照组比较中，C等位基因及C等位基因携带者（CC＋TC）基因型频率冠心病组明显高于正常对照组（C等位基因：57．050Avs．41．32％，P〈0．01；C等位基因携带者：79．32％vs．65．47％，P〈0．01）；与TT纯合子相比，（CC＋TC）基因型冠心病患病风险显著增加（OR=2．03，95％CI：1．53-2．80）。对性别进行亚组分析显示，无论男性还是女性人群中冠心病组C等位基因携带者频率均显著高于正常对照组（男性：79．63％vs．72．45％，P=0．02；女性：78．00％vs．51．50％，P〈0．01），C等位基因携带者冠心病患病风险明显高于TT型（男性：OR=1．48，95％C1：1．06-2．09；女性：OR=3．34，95％CI：1．90-5．86）。（2）与无支架内再狭窄组相比，支架内再狭窄组C等位基因频率及C等位基因携带者分布频率均显著升高（C等位基因频率：72．39％vs．54．84％，P〈O．01；CC＋TC型：89．55％vs．77．85％，P=0．027）。与TT纯合子相比，C等位基因携带者支架内再狭窄患病风险升高2．44倍（95％C1：1．08-5．50）。性别亚组分析表明，男性人群中支架内再狭窄组C等位基因携带者频率高于无支架内再狭窄组（92．86％vs．77．660A，P=0．008），C等位基因携带者发生支架内再狭窄的风险是TT型的3．74倍（95％CI：1．32-10．64），而在女性人群中两组间（CC＋TC）基因型分布频率无统计学意义（P=0．655）。结论CX37C等位基因不仅与冠心病的发生发展有关联，而且与男性PCI术后支架内再狭窄的发生发展相关。

Objective To assess the association between 1019C/T polymorphism of Connexin 37 （CX37） gene and susceptibility to restenosis after percutaneous coronary intervention （PC/） in ethnic Han Chinese patients from Wuxi. Methods Five hundred and thirty-two patients with coronary artery disease （CAD） who had undergone PC1 underwent coronary angiography （CAG） in 3 months, and were divided into in-stent restenosis （ISR） group （n=67） and no in-stent restenosis （NISR） group （n=465）. Five hundred and one healthy individuals have served as the control group. All cases were genotyped with DNA sequencing. Results Compared with healthy controls, the frequency of CX37 C allele was higher in CAD patients （57.05%vs. 41. 32%, P〈0.01）. The frequency of C carries （CC＋TC） was 79.32% in CAD patients, against 65.47% in healthy controls （P〈0.01）. The risk for CAD was significantly increased in carriers of C allele （CC＋TC） compared with TT homozygotes （OR=2.03, 95%CI： 1.53-2.80）. Stratified analysis has indicated a significant difference in the frequency of C allele carriers between both male and female CAD patients and healthy controls （79.63% vs. 72.45%, P：0.02;78.00% vs. 51.50%, P〈0.01）. For both genders, carriers of C allele had a higher risk for CAD compared with TT homozygotes （males： 0R=1.48, 95%CI： 1.06 2.09;females： OR=3.34, 95%CI： 1.90-5.86）. Compared withNISR group, the frequency of CX37 C allele and C carries （CC＋TC） were significantly higher in ISR group （72.39% vs. 54.84%, P〈0.01;89.55%vs. 77.85%, P=0.027）. Compared withTThomozygotes, the risk for restenosis has significantly increased in carriers of C allele （CC＋TC） （OR=2.44, 95%CI： 1.08- 5.50）. Stratified analysis also suggested that the frequency of C carriers was significantly higher in male ISR group compared with male NISR group （92. 860/oo vs. 77. 66%, P=0. 008）. The risk for restenosis has increased by nearly fouFfold in carriers of C allele （CC＋ TC） compared with TT homozygotes （95 % CI： 1.32 10.64）. However, for female patients, no significant difference was detected in the ISR risk between carriers of CC＋TC type and TT homozygotes （P = 0. 655）. Conclusion The C allele of 1019C/T polymorphism in the CX37 gene is associated with susceptibility to CAD as well as restenosis after coronary stenting in male patients from Wuxi.