Effects of Polymorphisms in APOA4-APOA5-ZNF259-BUD13 Gene Cluster on Plasma Levels of Triglycerides and Risk of Coronary Heart Disease in a Chinese Han Population

PLoS One. 2015 Sep 23;10(9):e0138652. doi: 10.1371/journal.pone.0138652. eCollection 2015.

Abstract

Background/aim: Recent genome-wide association studies have identified several loci influencing lipid levels. The present study focused on the triglycerides (TG)-associated locus, the APOA4-APOA5-ZNF259-BUD13 gene cluster on chromosome 11, to explore the role of genetic variants in this gene cluster in the development of increasing TG levels and coronary heart disease (CHD).

Methodology/principal findings: Six single nucleotide polymorphisms (SNPs), rs4417316, rs651821, rs6589566, rs7396835, rs964184 and rs17119975, in the APOA4-APOA5-ZNF259-BUD13 gene cluster were selected and genotyped in 5374 healthy Chinese subjects. There were strong significant associations between the six SNPs and TG levels (P < 1.0 × 10(-8)). Moreover, a weighted genotype score was found to be associated with TG levels (P = 3.28 × 10(-13)). The frequencies of three common haplotypes were observed to be significantly different between the high TG group and the low TG group (P < 0.05). However, no significant effects were found for the SNPs regarding susceptibility to CHD in the Chinese case-control populations.

Conclusions/significance: This study highlights the genotypes, genotype scores and haplotypes of the APOA4-APOA5-ZNF259-BUD13 gene cluster that were associated with TG levels in a Chinese population; however, the genetic variants in this gene cluster did not increase the risk of CHD in the Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Apolipoprotein A-V
  • Apolipoproteins A / genetics*
  • Asian People
  • Carrier Proteins / genetics*
  • China
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / pathology
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Membrane Transport Proteins
  • Middle Aged
  • Multigene Family
  • Polymorphism, Single Nucleotide*
  • RNA-Binding Proteins / genetics*
  • Risk Factors
  • Triglycerides / blood*

Substances

  • APOA5 protein, human
  • Apolipoprotein A-V
  • Apolipoproteins A
  • BUD13 homolog protein, human
  • Carrier Proteins
  • Membrane Transport Proteins
  • RNA-Binding Proteins
  • Triglycerides
  • ZPR1 protein, human
  • apolipoprotein A-IV

Grants and funding

This work is supported by the National Natural Scientific Foundation of China (NSFC-81202274), the Funds for outstanding young scholars in Chongqing Medical University to LZ (CYYQ201304), the Chongqing Natural Science Foundation (cstc2014jcyjA10015). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.