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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
Author(s) -
PerezMartinez Pablo,
DelgadoLista Javier,
GarciaRios Antonio,
Tierney Audrey C.,
Gulseth Hanne L.,
Williams Christine M.,
Karlström Brita,
KiećWilk Beata,
Blaak Ellen E.,
Helal Olfa,
Saris Wim H. M.,
Defoort Catherine,
Drevon Christian A.,
Lovegrove Julie A.,
DembinskaKieć Aldona,
Riserus Ulf,
Roche Helen M.,
LopezMiranda Jose
Publication year - 2012
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201100504
Subject(s) - insulin resistance , medicine , endocrinology , insulin , single nucleotide polymorphism , polyunsaturated fatty acid , insulin receptor , irs2 , genotype , metabolic syndrome , type 2 diabetes , fatty acid , allele , biology , diabetes mellitus , chemistry , gene , genetics , biochemistry
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.