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

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

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.

Delgado-Lista, Javier (author)
Garcia-Rios, Antonio (author)
Tierney, Audrey C. (author)
Gulseth, Hanne L. (author)
Williams, Christine M. (author)
Karlström, BritaUppsala universitet,Klinisk nutrition och metabolism(Swepub:uu)britkarl (author)
Kiec-Wilk, Beata (author)
Blaak, Ellen E. (author)
Helal, Olfa (author)
Saris, Wim H. M. (author)
Defoort, Catherine (author)
Drevon, Christian A. (author)
Lovegrove, Julie A. (author)
Dembinska-Kiec, Aldona (author)
Riserus, Ulf (author)
Roche, Helen M. (author)
Lopez-Miranda, Jose (author)
Uppsala universitetKlinisk nutrition och metabolism (creator_code:org_t)

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