A CpG-SNP Located within the ARPC3 Gene Promoter Is Associated with Hypertriglyceridemia in Severely Obese Patients

Ann Nutr Metab. 2016;68(3):203-12. doi: 10.1159/000445358. Epub 2016 Apr 8.

Abstract

Aims: To test the potential association of cytosine-phosphate-guanine dinucleotides (CpG)-single-nucleotide polymorphisms (SNPs) located within actin-related protein 2/3 complex subunit 3 (ARPC3), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obese patients.

Methods: Prioritized SNPs within the ARPC3 locus were genotyped and tested for associations with MetS features in a cohort of 1,749 obese patients with and without MetS. Association testing with CpG methylation levels was performed in a methylation sub-cohort of 16 obese men.

Results: A significant association was found between the CpG-SNP rs3759384 (C>T) and plasma triglyceride (TG) levels (false discovery rate-corrected p = 3.5 × 10-2), with 0.6% of the phenotypic variance explained by the CpG-SNP, and with TT homozygotes showing the highest plasma TG levels (1.89 mmol/l). The carriers of the rs3759384 T allele also showed a significant decrease in methylation levels of the ARPC3 promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. ARPC3 expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02).

Conclusions: The increased plasma TG levels found in homozygous rs3759384 T allele carriers argue for a relevant role of this CpG-SNP in lipid management among obese individuals, which may be driven by an epigenetic-mediated mechanism.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / blood
  • Actin-Related Protein 2-3 Complex / genetics*
  • Actin-Related Protein 2-3 Complex / metabolism
  • Adult
  • Alleles
  • Body Mass Index
  • Cohort Studies
  • DNA Methylation
  • Female
  • Gene Expression Regulation
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Homozygote
  • Humans
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / etiology
  • Hypertriglyceridemia / genetics
  • Hypertriglyceridemia / metabolism
  • Intra-Abdominal Fat / metabolism
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / physiopathology
  • Middle Aged
  • Obesity, Abdominal / complications
  • Obesity, Abdominal / etiology
  • Obesity, Abdominal / genetics
  • Obesity, Abdominal / metabolism
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Quebec
  • Severity of Illness Index

Substances

  • ARPC3 protein, human
  • Actin-Related Protein 2-3 Complex

Supplementary concepts

  • Abdominal obesity metabolic syndrome