title: Single nucleotide polymorphisms (SNPs) involved in insulin resistance, weight regulation, lipid metabolism and inflammation in relation to metabolic syndrome: an epidemiological study.
abstract: BACKGROUND
  Mechanisms involved in metabolic syndrome (MetS) development include insulin resistance, weight regulation, inflammation and lipid metabolism. Aim of this study is to investigate the association of single nucleotide polymorphisms (SNPs) involved in these mechanisms with MetS.
  
  
  METHODS
  In a random sample of the EPIC-NL study (n = 1886), 38 SNPs associated with waist circumference, insulin resistance, triglycerides, HDL cholesterol and inflammation in genome wide association studies (GWAS) were selected from the 50K IBC array and one additional SNP was measured with KASPar chemistry. The five groups of SNPs, each belonging to one of the metabolic endpoints mentioned above, were associated with MetS and MetS-score using Goeman's global test. For groups of SNPs significantly associated with the presence of MetS or MetS-score, further analyses were conducted.
  
  
  RESULTS
  The group of waist circumference SNPs was associated with waist circumference (P=0.03) and presence of MetS (P=0.03). Furthermore, the group of SNPs related to insulin resistance was associated with MetS score (P<0.01), HDL cholesterol (P<0.01), triglycerides (P<0.01) and HbA1C (P=0.04). Subsequent analyses showed that MC4R rs17782312, involved in weight regulation, and IRS1 rs2943634, related to insulin resistance were associated with MetS (OR 1.16, 95%CI 1.02-1.32 and OR 0.88, 95% CI 0.79; 0.97, respectively). The groups of inflammation and lipid SNPs were neither associated with presence of MetS nor with MetS score.
  
  
  CONCLUSIONS
  In this study we found support for the hypothesis that weight regulation and insulin metabolism are involved in MetS development.MC4R rs17782312 and IRS1 rs2943634 may explain part of the genetic variation in MetS.
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. cecile.povel@wur.nl
authors.forename: Cécile M
authors.initials: CM
authors.lastname: Povel
authors.forename: Jolanda M A
authors.initials: JM
authors.lastname: Boer
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Martijn E T
authors.initials: ME
authors.lastname: Dollé
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: van der Schouw
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D007333:Insulin Resistance / Q000235:genetics*; D016014:Linear Models; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D055105:Waist Circumference / Q000235:genetics
chemical_list: D015415:Biomarkers