Study of Five Pubertal Transition-Related Gene Polymorphisms as Risk Factors for Premature Coronary Artery Disease in a Chinese Han Population

Bin Chen; Fangyi Xie; Chengchun Tang; Genshan Ma; Li Wei; Zhong Chen

doi:10.1371/journal.pone.0136496

Study of Five Pubertal Transition-Related Gene Polymorphisms as Risk Factors for Premature Coronary Artery Disease in a Chinese Han Population

PLoS One. 2015 Aug 25;10(8):e0136496. doi: 10.1371/journal.pone.0136496. eCollection 2015.

Authors

Bin Chen¹, Fangyi Xie², Chengchun Tang³, Genshan Ma³, Li Wei⁴, Zhong Chen¹

Affiliations

¹ Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
² Central Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
³ Department of Cardiology, The Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Nanjing 210009, China.
⁴ Department of Endocrinology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.

Abstract

Background: Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.

Methods: We enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.

Results: The following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190-4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012-2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233-4.348, P = 0.015).

Conclusions: Among the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Asian People / genetics*
Case-Control Studies
Coronary Artery Disease / genetics*
Ethnicity / genetics*
Female
Genetic Predisposition to Disease*
Humans
Logistic Models
Male
Middle Aged
Multivariate Analysis
Polymorphism, Single Nucleotide / genetics*
Puberty / genetics*
Risk Factors

Grants and funding

The study was funded by Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (Dr. Li Wei), Pudong New Area Science and Technology Development Fund (PKJ2014-Y09), and Shanghai Municipal Commission of Health and Family Planning Research Project (201440309) (Dr. Zhong Chen). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.