炎症小体Nod样受体蛋白3及胱天蛋白酶募集域蛋白8基因多态性与急性冠脉综合征的相关性

Association of NLRP3 rs10754558 and CARD8 rs2043211 polymorphisms with the occurrence of acute coronary syndrome

目的 探讨Nod样受体蛋白3（NLRP3）rs10754558位点C〉G和胱天蛋白酶募集域蛋白8（CARD8）rs2043211位点A〉T多态性与急性冠脉综合征（ACS）发病的关系。方法 入选450例ACS患者和380例对照组人群,使用ABI Snapshot方法分析NLRP3rs10754558位点和CARD8rs2043211位点多态性;冠状动脉造影后以Gensini评分评价冠脉狭窄程度;Elisa测定血清白细胞介素-1β（IL-1β）浓度。结果 NLRP3rs10754558位点对照组和ACS组基因型频率比较差异有统计学意义（χ~2=7.64,P=0.022）,NLRP3rs10754558位点G等位基因与ACS发病相关（AOR=1.334,95%CI=1.085~1.642,P=0.006）。而CARD8rs2043211位点两组间基因型频率比较差异无统计学意义（χ~2=1.08,P=0.582）,且与ACS发病无明显关系（AOR=1.168,95%CI=0.942~1.449,P=0.156）。ACS患者NLRP3rs10754558位点GG基因型Gensini评分高于CC基因型（74.07±2.13 vs.42.91±1.80,P〈0.001）;IL-1β质量浓度GG基因型显著高于CC基因型[（3.21±2.68）pg/mL vs.（1.37±1.36）pg/mL,P〈0.001]。结论NLRP3rs10754558位点C〉G基因多态性与中国汉族人群ACS发病及冠状动脉狭窄程度有关;G等位基因是ACS发病的危险等位基因,其作用与IL-1β浓度升高有关。

Objective To investigate the potential association of the Nodlike receptor protein 3 （NLRP3） rs10754558 and caspase recruitment domain-containing protein 8 （CARD8） rs2043211 SNPs with the occurrence of acute coronary syndrome （ACS）. Methods The NLRP3 rs10754558 and CARD8 rs2043211 SNPs were analyzed using the ABI PRISM-Snapshot multiplex method in 450 Chinese Han patients with ACS and 380 controls in the case- control study. Coronary angiography was performed to evaluate the severity of coronary atherosclerosis by Gensini score. The content of IL-1β in serum was determined by ELISA. Results The difference in rs10754558 allele frequency between the control group and the ACS group was significant （ x2 = 7.64, P = 0. 022）. The NLRP3 rs10754558 G allele was significantly associated with the occurrence of ACS （AOR= 1. 334, 95% CI = 1. 085 - 1. 642, P = 0. 006）, while CARD8 rs2043211 polymorphism was not involved （ x2 = 1.08, P = 0. 582）. Patients with GG genotype of NLRP3 rs10754558 had a higher Gensini score than those with＇CC genotype （74.07± 2.13 vs. 42.91±1.80, P〈0. 001）. There was no significant difference in Gensini score among ACS patients with different genotypes of CARD8 rs2043211. In the ACS group, the level of IL-1β in patients with GG genotype of NLRP3 rs10754558 was significantly higher than those patients with CC genotype （3.21±2.68 vs. 1. 37±1.36 pg/mL, P〈 0. 001）. Conclusion The NLRP3 rs10754558 nolvmornhism is involved in the occurrence of ACS and the severityof coronary atherosclerosis in the Chinese Han population. G allele is the risk allele of ACS. The role of G allele may be associated with elevated level of IL-1β.