Common polymorphisms in the PPARγ2 and IRS-1 genes and their interaction influence serum adiponectin concentration in young Finnish men

The Gly972Arg substitution of the insulin receptor substrate-1 (IRS-1) gene and the Pro12Pro genotype of the peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) gene have been suggested to be associated with type 2 diabetes mellitus. In this study, the influence of these two polymorphisms on serum adiponectin concentrations was investigated. The Pro12Ala polymorphism of the PPAR gamma 2 gene and the Gly972Arg polymorphism of the IRS-1 gene were genotyped in 252 young Finnish servicemen. The Ala12Ala genotype of PPAR gamma 2 was associated with a higher adiponectin level compared to the Pro12Ala genotype (P=0.02) and the Pro12Pro genotype (p=0.02). Total (p=0.02) and low-density lipoprotein (LDL) cholesterol (p=0.03) levels were higher in subjects with the Pro12Pro genotype compared to the Pro12Ala genotype. No difference was observed in serum adiponectin level between the IRS-1 genotype groups. The subjects with X972Arg of this gene had high total and LDL cholesterol levels (p < 0.05). The interaction between the PPAR gamma 2 and IRS-1 genes with respect to their effects on adiponectin levels was statistically significant (p=0.02). Adiponectin was significantly higher (p < 0.05) in subjects who simultaneously had the Ala/Ala (PPAR gamma 2)+Gly/Gly (IRS-1) genotype combination compared to subjects with the Pro/Pro + Gly/Gly and Pro/Ala + Gly/Gly genotype combinations. Total and LDL cholesterol was higher (p < 0.05) in subjects with Pro/Pro + X/Arg compared to subjects with the two before mentioned genotype combinations. We conclude that the Ala12Ala genotype of PPAR gamma 2 is associated with elevated adiponectin level, and that the PPAR gamma 2 and IRS-1 genes have a possible interaction in their effects on adiponectin concentration. (c) 2004 Elsevier Inc. All rights reserved.