Genetic Variants in PCSK1 Gene Are Associated with the Risk of Coronary Artery Disease in Type 2 Diabetes in a Chinese Han Population: A Case Control Study

Abstract

Background

Insulin and glucagon-like peptide 1 (GLP-1), converted by proprotein convertase 1 (PC1/3) from proinsulin and proglucagon, are associated with type 2 diabetes (T2DM) and coronary artery disease (CAD). The aim of this study is to investigate the association of PCSK1 gene, which encodes PC1/3, with the risk of CAD in Chinese patients with T2DM.

Methods

We selected and genotyped 5 haplotype-tagging single nucleotide polymorphisms (SNPs) at PCSK1 gene (across 39873bp locus) in a case-control study of Chinese Han population involving 425 diabetic patients (62.1% male, mean age 63.2 years) with CAD as positive cases and 258 diabetic patients (44.2% male, mean age 62.0 years) without CAD as controls.

Results

The allele frequencies at rs3811951 were significantly different between cases and controls (30.7% vs. 37.2%), with the allele G associated with decreased risk for CAD (OR = 0.75, 95% CI = 0.59–0.94, p = 0.013). In recessive inheritance mode, the carriers of GG had a lower risk (OR = 0.50, 95%CI = 0.31–0.82, p = 0.005), even after adjusted for gender, age, BMI and smoking (OR = 0.43, 95%CI = 0.24–0.77, p = 0.004). The carriers of the minor allele A at rs156019 had a higher risk (OR = 1.66, 95%CI = 1.10–2.50, p = 0.016 after adjustment) in dominant inheritance mode. The SNP rs6234 was also significantly associated with CAD risk in women, with the carriers of the minor allele G at rs6234 associated with a reduced CAD risk in recessive inheritance mode (OR = 0.42, 95% CI = 0.18–0.95, p = 0.036 after adjustment).

Conclusions

Our results found that common genetic variants in PCSK1 were associated with CAD in Chinese patients with T2DM.

Contributors

Joseph Devaney: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 28 January 2014

Volume: 9

Issue: 1

Affiliations

[1]Department of Endocrinology, Peking University First Hospital, Beijing, China

Children's National Medical Center, Washington, United States of America

Author notes

* E-mail: mxiaowei@ 123456yahoo.com

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: XM. Performed the experiments: XW. Analyzed the data: XW. Contributed reagents/materials/analysis tools: RL GB JZ RD NG NF XG. Wrote the paper: XW XM. Collected information: RL GB JZ RD NG NF.

Article

Publisher ID: PONE-D-13-37902

DOI: 10.1371/journal.pone.0087168

PMC ID: 3904973

SO-VID: e6b2cfed-b824-4a69-a75f-cbf27e2862ce

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Page count

Pages: 6

Funding

The study was granted by National 973 project (2006CB503903, 2006CB503908) in China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Categories

Subject: Research Article

Subject: Biology

Subject: Genetics

Subject: Population Genetics

Subject: Genetic Polymorphism

Subject: Medicine

Subject: Anatomy and Physiology

Subject: Cardiovascular System

Subject: Endocrine System

Subject: Cardiovascular

Subject: Atherosclerosis

Subject: Coronary Artery Disease

Subject: Valvular Disease

Subject: Clinical Genetics

Subject: Gene Therapy

Subject: Endocrinology

Subject: Diabetic Endocrinology

Subject: Diabetes Mellitus Type 2