Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease

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.