Novel polymorphism of the HMGCR gene related to the risk of diabetes in premature triple-vessel disease patients

J Gene Med. 2022 Sep;24(9):e3445. doi: 10.1002/jgm.3445. Epub 2022 Sep 4.

Abstract

Background: Coronary heart disease and diabetes are highly interrelated and complex diseases. We proposed to investigate the association of genetic polymorphisms of the lipoprotein important regulatory genes Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with premature triple-vessel coronary disease (PTVD) with diabetes, blood glucose and body mass index.

Methods: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183 and rs2073547) of NPC1L1 and three SNPs (rs12916, rs2303151 and rs4629571) of HMGCR were genotyped in 872 PTVD patients.

Results: After performing logistic regression analysis adjusted for age and sex, rs2303151 of HMGCR was related to the risk of diabetes in the dominance model (odds ratio = 1.35, 95% confidence interval = 1.01-1.80, p = 0.04). However, the four SNPs of NPC1L1 were not associated with the risk of diabetes. Further analyses showed that neither the above SNPs of NPC1L1, nor the SNPs of HMGCR were related to blood glucose and body mass index (all p > 0.05).

Conclusions: We report that rs2303151 is a novel polymorphism of the HMGCR gene related to the risk of diabetes in PTVD patients, which suggests HMGCR may be a potential common targeted pathogenic pathways between coronary heart disease and diabetes.

Keywords: HMGCR; NPC1L1; diabetes; genetic variants; premature triple-vessel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose
  • Cholesterol, LDL / genetics
  • Coenzyme A / genetics
  • Coronary Artery Disease* / genetics
  • Diabetes Mellitus*
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics*
  • Membrane Transport Proteins / genetics
  • Oxidoreductases / genetics
  • Polymorphism, Single Nucleotide

Substances

  • Blood Glucose
  • Cholesterol, LDL
  • Membrane Transport Proteins
  • Oxidoreductases
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases
  • Coenzyme A