Three-vessel disease (TVD) is a severe coronary heart disease (CHD) with poor prognosis. Niemann-Pick C1-like 1 (NPC1L1) is a transporter protein for exogenous cholesterol absorption, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is a rate-limiting enzyme for cholesterol synthesis. We aimed to investigate the association between NPC1L1 and HMGCR 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 NPC1L1 gene and four SNPs, rs12916, rs2303151, rs2303152, and rs4629571, on HMGCR gene were genotyped. Multivariate logistic regression analysis showed that rs4720470 of NPC1L1 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, p = 0.044), and that rs2303151 of HMGCR was associated with higher in recessive (OR: 3.383; 95% CI: 1.040–10.998, p = 0.043) and codominant (OR: 1.458; 95% CI: 1.038–2.047, p = 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; p = 0.021). We reported for the first time that the rs4720470 on NPC1L1 gene and rs2303151 on HMGCR gene were associated with risk of 1-year MACCE in TVD.

中文翻译：

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NPC1L1 和 HMGCR 基因多态性与三支血管疾病患者主要不良心脑血管事件的相关性

三支血管疾病（TVD）是一种预后较差的严重冠心病（CHD）。Niemann-Pick C1-like 1 ( 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。我们旨在调查NPC1L1和HMGCR之间的关联TVD患者的基因多态性和主要不良心脑血管事件（MACCE）。共有342例TVD患者作为TVD事件组连续入组并随访1年MACCE（全因死亡、心肌梗死、血运重建、再入院和卒中），344例无冠心病患者为对照组。对NPC1L1基因上的四个单核苷酸多态性 (SNP) rs11763759、rs4720470、rs2072183 和 rs2073547和HMGCR基因上的四个单核苷酸多态性 rs12916、rs2303151、rs2303152 和 rs4629571 进行基因分型。多因素logistic回归分析显示NPC1L1的rs4720470在共显性模型中与 MACCE 的 TVD 风险较高相关（优势比 [OR]：1.315；95% 置信区间 [CI]：1.007-1.716，p  = 0.044），并且HMGCR的 rs2303151 与隐性较高的风险相关（ OR：3.383；95% CI：1.040–10.998，p  = 0.043）和共显性（OR：1.458；95% CI：1.038–2.047，p  = 0.030）模型。具有共显性模型中变异 rs4720470 和隐性模型中变异 rs2303151 的患者与较高风险相关（OR：6.772，CI：1.338-34.280；p  = 0.021）。我们首次报道了NPC1L1基因上的 rs4720470 和HMGCR基因上的 rs2303151 与 TVD 的 1 年 MACCE 风险相关。