Zhao Xueyan, Li Jiawen, Tang Xiaofang, Liu Ru, Xu Jingjing, Xu Lianjun, Jiang Lin, Huang Keyong, Tian Jian, Feng Xinxing, Wu Yajie, Zhang Yin, Wang Dong, Sun Kai, Xu Bo, Zhao Wei, Hui Rutai, Gao Runlin, Song Lei, Yuan Jinqing
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Hum Gene Ther. 2021 Jun;32(11-12):581-588. doi: 10.1089/hum.2020.229. Epub 2021 Jan 22.
Three-vessel disease (TVD) is a severe coronary heart disease (CHD) with poor prognosis. Niemann-Pick C1-like 1 () is a transporter protein for exogenous cholesterol absorption, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase () is a rate-limiting enzyme for cholesterol synthesis. We aimed to investigate the association between and gene polymorphisms and major adverse cardiac and cerebrovascular events (MACCE) in patients with TVD. A total of 342 TVD patients were consecutively enrolled and followed up for 1-year MACCE (a composite of all-cause death, myocardial infarction, revascularization, readmission, and stroke) as TVD event group, and 344 patients without CHD were control group. Four single-nucleotide polymorphisms (SNPs), rs11763759, rs4720470, rs2072183, and rs2073547, on gene and four SNPs, rs12916, rs2303151, rs2303152, and rs4629571, on gene were genotyped. Multivariate logistic regression analysis showed that rs4720470 of was associated with higher risk of TVD with MACCE in codominant model (odds ratio [OR]: 1.315; 95% confidence intervals [CI]: 1.007-1.716, = 0.044), and that rs2303151 of was associated with higher in recessive (OR: 3.383; 95% CI: 1.040-10.998, = 0.043) and codominant (OR: 1.458; 95% CI: 1.038-2.047, = 0.030) model, respectively. Patients with both variant rs4720470 in codominant model and variant rs2303151 in recessive model related to a higher risk (OR: 6.772, CI: 1.338-34.280; = 0.021). We reported for the first time that the rs4720470 on gene and rs2303151 on gene were associated with risk of 1-year MACCE in TVD.
三支血管病变(TVD)是一种预后较差的严重冠心病(CHD)。尼曼-匹克C1样1蛋白(NPC1L1)是外源性胆固醇吸收的转运蛋白,3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)是胆固醇合成的限速酶。我们旨在研究NPC1L1和HMGCR基因多态性与TVD患者主要不良心脑血管事件(MACCE)之间的关联。连续纳入342例TVD患者作为TVD事件组,随访1年的MACCE(全因死亡、心肌梗死、血运重建、再入院和中风的综合指标),344例无CHD患者作为对照组。对NPC1L1基因上的4个单核苷酸多态性(SNP),即rs11763759、rs4720470、rs2072183和rs2073547,以及HMGCR基因上的4个SNP,即rs12916、rs2303151、rs2303152和rs4629571进行基因分型。多因素逻辑回归分析显示,NPC1L1基因的rs4720470在共显性模型中与TVD合并MACCE的较高风险相关(比值比[OR]:1.315;95%置信区间[CI]:1.007-1.716,P = 0.044),HMGCR基因的rs2303151在隐性模型(OR:3.383;95% CI:1.040-10.998,P = 0.043)和共显性模型(OR:1.458;95% CI:1.038-2.047,P = 0.030)中分别与较高风险相关。共显性模型中携带rs4720470变异和隐性模型中携带rs2303151变异的患者相关风险更高(OR:6.772,CI:1.338-34.280;P = 0.021)。我们首次报道NPC1L1基因上的rs4720470和HMGCR基因上的rs2303151与TVD患者1年MACCE风险相关。