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
T2 - Association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels and insulin resistance
AU - Tierney, Audrey
AU - Perez-Martinez, Pablo
AU - Delgado-Lista, Javier
AU - Garcia-Rios, Antonio
AU - Gulseth, Hanne L.
AU - Williams, Christine M.
AU - Karlström, Brita
AU - Kieć-Wilk, Beata
AU - Blaak, Ellen E.
AU - Helal, Olfa
AU - Saris, Wim H.M.
AU - Defoort, Catherine
AU - Drevon, Christian A.
AU - Lovegrove, Julie A.
AU - Dembinska-Kieć, Aldona
AU - Riserus, Ulf
AU - Roche, Helen M.
AU - Lopez-Miranda, Jose
PY - 2012/2
Y1 - 2012/2
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 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.
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 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.
KW - Fatty acids
KW - Metabolic syndrome
KW - N-3 PUFA
KW - Nutrigenomics
KW - Polymorphism
UR - http://www.scopus.com/inward/record.url?scp=84858330242&partnerID=8YFLogxK
U2 - 10.1002/mnfr.201100504
DO - 10.1002/mnfr.201100504
M3 - Article
C2 - 22147666
AN - SCOPUS:84858330242
SN - 1613-4125
VL - 56
SP - 309
EP - 315
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 2
ER -