Association of NPC1L1 and HMGCR Gene Polymorphisms with Coronary Artery Calcification in Patients with Premature Triple-vessel Coronary Disease

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2024 Jan 17

PMID 38233830

Authors

Yulong Li

Jiawen Li

Xiaofang Tang

Jingjing Xu

Ru Liu

Lin Jiang

Jian Tian

Yin Zhang

Dong Wang

Kai Sun

Bo Xu

Wei Zhao

Rutai Hui

Runlin Gao

Lei Song

Jinqing Yuan

Xueyan Zhao

Affiliations

Soon will be listed here.

Abstract

Background: Coronary artery calcification (CAC) is a highly specific marker of atherosclerosis. Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are the therapeutic targets of ezetimibe and statins, respectively, which are important for the progression of atherosclerosis. However, CAC's genetic susceptibility with above targets is still unknown. We aimed to investigate the association of NPC1L1 and HMGCR gene polymorphisms with CAC in patients with premature triple-vessel disease (PTVD).

Methods: Four single nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, rs2073547) of NPC1L1, and three SNPs (rs12916, rs2303151, rs4629571) of HMGCR were genotyped in 872 PTVD patients. According to the coronary angiography results, patients were divided into low-degree CAC group and high-degree CAC group.

Results: A total of 872 PTVD patients (mean age, 47.71 ± 6.12; male, 72.8%) were finally included for analysis. Multivariate logistic regression analysis showed no significant association between the SNPs of NPC1L1 and HMGCR genes and high-degree CAC in the total population (P > 0.05). Subgroup analysis by gender revealed that the variant genotype (TT/CT) of rs4720470 on NPC1L1 gene was associated with increased risk for high-degree CAC in male patients only (OR = 1.505, 95% CI: 1.008-2.249, P = 0.046) in dominant model, but no significant association was found in female population, other SNPs of NPC1L1 and HMGCR genes (all P > 0.05).

Conclusions: We reported for the first time that the rs4720470 on NPC1L1 gene was associated with high-degree CAC in male patients with PTVD. In the future, whether therapies related to this target could reduce CAC and cardiovascular events deserves further investigation.

Citing Articles

From Cells to Plaques: The Molecular Pathways of Coronary Artery Calcification and Disease.

Mitsis A, Khattab E, Christodoulou E, Myrianthopoulos K, Myrianthefs M, Tzikas S J Clin Med. 2024; 13(21).

PMID: 39518492 PMC: 11545949. DOI: 10.3390/jcm13216352.

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