Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: association with plasma fatty acid levels and insulin resistance

Perez-Martinez , P., Delgado-Lista , J., Garcia-Rios , A., Gulseth , H., Williams, C., Drevon, C., Lovegrove, J. ORCID: https://orcid.org/0000-0001-7633-9455, Roche, H. and Lopez-Miranda, J. (2012) Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: association with plasma fatty acid levels and insulin resistance. Molecular Nutrition & Food Research, 56 (2). pp. 309-315. ISSN 1613-4125 doi: 10.1002/mnfr.201100504

Abstract/Summary

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.