Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion-CIBEROBN, Instituto de Salud Carlos, Cordoba, Spain.
Mol Nutr Food Res. 2012 Feb;56(2):309-15. doi: 10.1002/mnfr.201100504. Epub 2011 Dec 7.
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.
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.
The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects.
已有多项研究探讨了胰岛素受体底物-2（IRS-2）多态性与胰岛素抵抗和 2 型糖尿病之间的关系。本研究旨在检验 IRS-2 基因座的遗传多态性是否与代谢综合征（MetS）患者的胰岛素抵抗程度和血浆脂肪酸水平相关。
本研究在 452 例 MetS 患者中测定了胰岛素敏感性、胰岛素分泌、葡萄糖效应、血浆脂肪酸组成和三个 IRS-2 标签单核苷酸多态性（SNP）。在 MUFA（单不饱和脂肪酸）水平最低（低于中位数）的患者中，与携带次要 G-等位基因（A/G 和 G/G）的患者相比，rs2289046 A/A 基因型与较低的葡萄糖效应（p<0.038）、较高的空腹胰岛素浓度（p<0.028）和较高的 HOMA-IR（p<0.038）相关。相比之下，在 MUFA 水平最高（高于中位数）的患者中，A/A 基因型与较低的空腹胰岛素浓度和 HOMA-IR 相关，而携带 G 等位基因且ω-3 多不饱和脂肪酸水平最高（高于中位数）的个体则表现出较低的空腹胰岛素（p<0.01）和 HOMA-IR（p<0.02），与 A/A 患者相比。
IRS2 基因座的 rs2289046 多态性可能通过与 MetS 患者特定的血浆脂肪酸相互作用影响胰岛素敏感性。
