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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (Ireland)
Pages (from-to)309-315
Number of pages7
JournalMolecular Nutrition and Food Research
Volume56
Issue number2
DOIs
Publication statusPublished - Feb 2012

Keywords

  • Fatty acids
  • Metabolic syndrome
  • N-3 PUFA
  • Nutrigenomics
  • Polymorphism

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