Genome-wide association study of coronary artery calcification in asymptomatic Korean populations

PLoS One. 2019 Mar 28;14(3):e0214370. doi: 10.1371/journal.pone.0214370. eCollection 2019.

Abstract

Epidemiologic evidence indicates that the prevalence and severity of coronary artery disease vary depending on ethnicity. In this study, a genome-wide association study for coronary artery calcification (CAC) was performed in a Korean population-based sample of 400 subjects without prior coronary artery disease and replicated in another of 1,288 subjects. CAC score, as assessed by multi-detector computed tomography, was evaluated in volunteers for screening purposes as part of a routine health examination. CAC score greater than the 90th percentile across the age in each sex group was considered severe CAC. Single nucleotide polymorphisms (SNPs) associated with severe CAC after adjusting for age, sex, hypertension, and diabetes were investigated using the additive model of logistic regression. One SNP (rs10757272 in the intronic region of the CDKN2B-AS1 gene in chromosome 9p21.3) met Bonferroni correction in the discovery set (p = 7.55E-08) and was also significant in the validation set by TaqMan assay (p = 0.036). Subjects with rs10757272 were found to have an increased odds ratio (OR) of having severe CAC in multivariate logistic regression analysis after adjusting for age, sex, hypertension, and diabetes (adjusted OR 3.24 and 95% CI 2.11-4.97). In conclusion, SNP rs10757272 in chromosome 9p21.3 was associated with severe CAC based on age and sex in an asymptomatic community-based Korean population. Therefore, it was associated with promotion of coronary artery calcification in subclinical state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics*
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / pathology*
  • Female
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • RNA, Long Noncoding / genetics
  • Republic of Korea
  • Retrospective Studies
  • Severity of Illness Index
  • Tomography, X-Ray Computed
  • Vascular Calcification / genetics
  • Vascular Calcification / pathology*

Substances

  • CDKN2B antisense RNA, human
  • RNA, Long Noncoding

Associated data

  • figshare/10.6084/m9.figshare.7850981

Grants and funding

This work was supported by the Technology Innovation Program (10050154, Business Model Development for Personalized Medicine Based on Integrated Genome and Clinical Information) funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea). Eunsoon Shin and Jong-Eun Lee are employed by DNA Link, Inc. DNA Link, Inc. provided support in the form of salaries for authors ES and J-EL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.