NPR-C gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a multicenter study

Abstract

To find a new locus that confers significant susceptibility to CAD in Chinese Han population, a genome-wide association study in 200 “extreme individuals” from a Shandong cohort and a pathway-based candidate gene study from a Shanghai cohort (293 CAD/293 controls) were simultaneously performed. Amongst them, 13 SNPs associated with CAD were selected to conduct validation and replication studies in additional 3363 CAD patients and 3148 controls. A novel locus rs700926 in natriuretic peptide receptor C (NPR-C) was identified in Shandong and Hubei cohorts. Then rs700926 and other nine tag SNPs were genotyped in four geographically different populations (Shandong, Shaanxi, Hubei and Sichuan cohorts), and 6 SNPs (rs700926, rs1833529, rs2270915, rs17541471, rs3792758 and rs696831) showed stronger association with CAD, regardless of single or combined analysis. We further genotyped rs2270915 and 10 additional tag SNPs in a central China cohort and identified rs12697273 and rs10066436 as the loci associated with CAD. All these positive associations remained significant after adjustment for traditional risk factors of CAD. NPR-C gene SNPs significantly contribute to CAD susceptibility in the Chinese Han population.

Meta-Analysis of Dilated Cardiomyopathy Using Cardiac RNA-Seq Transcriptomic Datasets

“…NPR3 (also known as NPR-C) encodes one of three receptors of natriuretic peptide which are small peptides responsible for regulating blood volume and pressure [29]. Several variations of NPR3 have been previously shown to be related to essential hypertension and coronary artery disease [30,31]. Follow-up functional studies are needed to investigate the mechanisms by which these genes contribute to the development of cardiomyopathy.…”

Pulmonary Arterial Hypertension Due to NPR-C Mutation: A Novel Paradigm for Normal and Pathologic Remodeling?

“…NPR-C signal transduction may also play an important role in the pathogenesis of atherosclerosis [17]. Recently, several novel single nucleotide polymorphisms (SNPs) of NPR-C were identified to be associated with atherosclerotic cardiovascular disease (ASCVD) in Han Chinese population [40]. Interestingly, multivariate logistical regression analysis demonstrated that the association between these SNPs and ASCVD remained significant even after adjustment for all the conventional risk factors of ASCVD including hypertension [40].…”

“…Recently, several novel single nucleotide polymorphisms (SNPs) of NPR-C were identified to be associated with atherosclerotic cardiovascular disease (ASCVD) in Han Chinese population [40]. Interestingly, multivariate logistical regression analysis demonstrated that the association between these SNPs and ASCVD remained significant even after adjustment for all the conventional risk factors of ASCVD including hypertension [40]. Although the underlying molecular mechanisms of the association between NPR-C gene polymorphism and ASCVD are unclear, some studies have shown that percutaneous coronary intervention-induced injury to neointima may lead to an increase in NPR-C expression in neointimal smooth muscle cells [17].…”

Prospective association of a genetic risk score with major adverse cardiovascular events in patients with coronary artery disease

“…[ 3 ] Using genome-wide association study (GWAS), more than 57 loci have been identified that contribute to risk of CAD or its major complication, myocardial infarction (MI). [ 4 – 9 ] Many of these loci are associated with known risks factors for CAD, such as low-density lipoprotein cholesterol (LDL-C) levels and blood pressure, which are the primary treatment targets for patients with CAD. However, the associations between these variants and clinical outcome of CAD were evaluated in comparatively few studies.…”