Riemann Pick C1 like 1 (NPC1L1) is involved in dietary cholesterol absorption and 3 hydroxy 3 methylglutaryl coenzyme A reductase (HMGCR) is target of statins that both play an important role on dyslipidemia in coronary heart disease. The aim of this study was to evaluate whether NPC1L1 and HMGCR genetic variants are associated with premature triple-vessel disease (PTVD).

Four single-nucleotide polymorphisms (rs11763759, rs4720470, rs2072183, rs2073547) of NPC1L1; and three single-nucleotide polymorphisms (rs12916, rs2303151, rs4629571) of HMGCR were genotyped in PTVD patients (n=872), and control subjects (n=401) (males ≤ 50 years old and females ≤ 60 years old) using the improved multiplex ligase detection reaction method.

A total of 1273 persons were finally included. The allele frequencies of rs12916 C of HMGCR and rs4720470 T of NPC1L1 were significantly higher in PTVD group than in the control group (all p<0.05). After performed logistic regression analysis adjusted for age and sex, rs12916 of HMGCR was still associated with the risk of PTVD in dominance model (odds ratio [OR] = 1.68, 95%confidence intervals[CI]: 1.29-2.18, p<0.001), recessive model (OR=1.43, 95% CI: 1.08-1.90, p=0.013 and additive model (OR = 1.38, 95% CI: 1.17-1.63, p<0.001); meanwhile, rs4720470 of NPC1L1 was associated with increased risk of PTVD in recessive model (OR = 1.74, 95% CI: 1.14-2.74, p=0.013).

Polymorphisms of the HMGCR gene and NPC1L1 gene are associated with the risk of PTVD in Chinese population. It is possible to bring more new possibilities to PTVD treatment strategy, drug development in the future.