TY - JOUR
T1 - 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
AU - Perez Martinez, P.
AU - Delgado Lista, J.
AU - Garcia Rios, A.
AU - Tierney, A.C.
AU - Gulseth, H.L.
AU - Williams, C.M.
AU - Karlstrom, B.
AU - Kiec-Wilk, B.
AU - Blaak, E.E.
AU - Helal, O.
AU - Saris, W.H.
AU - Defoort, C.
AU - Drevon, C.A.
AU - Lovegrove, J.A.
AU - Dembinska-Kiec, A.
AU - Riserus, U.
AU - Roche, H.M.
AU - Lopez Miranda, J.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
U2 - 10.1002/mnfr.201100504
DO - 10.1002/mnfr.201100504
M3 - Article
C2 - 22147666
SN - 1613-4125
VL - 56
SP - 309
EP - 315
JO - Molecular Nutrition & Food Research
JF - Molecular Nutrition & Food Research
IS - 2
ER -