A preliminary study of the relationship between promoter methylation of the ABCG1, GALNT2 and HMGCR genes and coronary heart disease

PLoS One. 2014 Aug 1;9(8):e102265. doi: 10.1371/journal.pone.0102265. eCollection 2014.

Abstract

Aims: To investigate the association of ABCG1, GALNT2 and HMGCR genes promoter DNA methylation with coronary heart disease (CHD) and explore the interaction between their methylation status and the CHD patients' clinical characteristics in Han Chinese population.

Methods and results: Methylation-specific polymerase chain reaction (MSP) technology was used to examine the role of the aberrant gene promoter methylation in CHD in Han Chinese population. A total of 85 CHD patients and 54 participants without CHD confirmed by angiography were recruited. 82.8% of the participants with ABCG1 gene promoter hypermethylation have CHD, while only 17.4% of the participants without hypermethylation have it. The average age of the participants with GALNT2 gene promoter hypermethylation is 62.10 ± 8.21, while that of the participants without hypermethylation is 57.28 ± 9.87; in the former group, 75.4% of the participants have CHD, compared to only 50% in the latter group. As for the HMGCR gene, the average age of the participants with promoter hypermethylation is 63.24 ± 8.10 and that of the participants without hypermethylation is 57.79 ± 9.55; its promoter hypermethylation is likely to be related to smoking. Our results indicated a significant statistical association of promoter methylation of the ABCG1 gene with increased risk of CHD (OR = 19.966; 95% CI, 7.319-54.468; P*<0.001; P*: adjusted for age, gender, smoking, lipid level, hypertension, and diabetes). Similar results were obtained for that of the GALNT2 gene (OR = 2.978; 95% CI, 1.335-6.646; P* = 0.008), but not of HMGCR gene (OR = 1.388; 95% CI, 0.572-3.371; P* = 0.469).

Conclusions: The present work provides evidence to support the association of promoter DNA methylation status with the risk profile of CHD. Our data indicates that promoter DNA hypermethylation of the ABCG1 and GALNT2 genes, but not the HMGCR gene, is associated with an increased risk of CHD. CHD, smoking and aging are likely to be the important factors influencing DNA hypermethylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / genetics*
  • Aged
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Coronary Disease / genetics*
  • Coronary Disease / metabolism
  • DNA Methylation*
  • Female
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics*
  • Male
  • Middle Aged
  • N-Acetylgalactosaminyltransferases / genetics*
  • Polypeptide N-acetylgalactosaminyltransferase
  • Promoter Regions, Genetic*
  • Risk

Substances

  • ABCG1 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Biomarkers
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases
  • N-Acetylgalactosaminyltransferases

Grants and funding

The research was supported by the grants from: Advanced Key Scientific and Technological Programs of NingBo (2011C51001), Fund of NingBo Science and Technology Innovation team (2011B82015), Natural Science Foundation of the Zhejiang Province (LY13H020008), Ningbo Personnel Training Project (first level), and the Project of Ningbo Medicine and Science (2009A02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.