Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: Association with plasma monounsaturated andn-3 polyunsaturated fatty acid levels and insulin resistance Academic Article uri icon


  • SCOPE: Several insulin receptor substrate-2 (IRS-2) polymorphisms have been studied in relation to insulin resistance and type 2 diabetes. To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS) subjects. METHODS AND RESULTS: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma fatty acid composition and three IRS-2 tag-single nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among subjects with the lowest level of monounsaturated (MUFA) (below the median), the rs2289046 A/A genotype was associated with lower glucose effectiveness (p<0.038), higher fasting insulin concentrations (p<0.028) and higher HOMA IR (p<0.038) as compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR, whereas individuals carrying the G allele and with the highest level of ω-3 polyunsaturated fatty acids (above the median) showed lower fasting insulin (p<0.01) and HOMA-IR (p<0.02) as compared with A/A subjects. CONCLUSION: The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects.


  • Perez-Martinez, Pablo
  • Delgado-Lista, Javier
  • Garcia-Rios, Antonio
  • Tierney, Audrey C
  • Gulseth, Hanne L
  • Williams, Christine M
  • Karlström, Brita
  • Kieć-Wilk, Beata
  • Blaak, Ellen E
  • Helal, Olfa
  • Saris, Wim HM
  • Defoort, Catherine
  • Drevon, Christian A
  • Lovegrove, Julie A
  • Dembinska-Kieć, Aldona
  • Riserus, Ulf
  • Roche, Helen M
  • Lopez-Miranda, Jose

publication date

  • February 2012