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

P. Perez Martinez, J. Delgado Lista, A. Garcia Rios, A.C. Tierney, H.L. Gulseth, C.M. Williams, B. Karlstrom, B. Kiec-Wilk, E.E. Blaak, O. Helal, W.H. Saris, C. Defoort, C.A. Drevon, J.A. Lovegrove, A. Dembinska-Kiec, U. Riserus, H.M. Roche, J. Lopez Miranda*

*Corresponding author for this work

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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 omega-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
Pages (from-to)309-15
JournalMolecular Nutrition & Food Research
Issue number2
Publication statusPublished - 1 Jan 2012

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