title: A CpG-SNP Located within the ARPC3 Gene Promoter Is Associated with Hypertriglyceridemia in Severely Obese Patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Nutrition and Functional Foods (INAF), Laval University, Quebec, QC, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: de Toro-Martín
authors.forename: Frédéric
authors.initials: F
authors.lastname: Guénard
authors.forename: André
authors.initials: A
authors.lastname: Tchernof
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
authors.forename: Simon
authors.initials: S
authors.lastname: Biron
authors.forename: Odette
authors.initials: O
authors.lastname: Lescelleur
authors.forename: Laurent
authors.initials: L
authors.lastname: Biertho
authors.forename: Simon
authors.initials: S
authors.lastname: Marceau
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011792:Quebec; D012720:Severity of Illness Index
chemical_list: C517043:ARPC3 protein, human; D051376:Actin-Related Protein 2-3 Complex