Authors: N Stefan F Machicao H Staiger J Machann F Schick O Tschritter C Spieth C Weigert A Fritsche M Stumvoll H U Häring
Publish Date: 2005/10/05
Volume: 48, Issue: 11, Pages: 2282-2291
Abstract
The adipokine adiponectin has insulinsensitising antiatherogenic and antiinflammatory properties Recently the genes for mouse and human adiponectin receptor1 ADIPOR1 and 2 ADIPOR2 have been cloned The aim of this study was to investigate whether genetic variants of the genes encoding ADIPOR1 and ADIPOR2 play a role in human metabolismWe screened ADIPOR1 and ADIPOR2 for polymorphisms and determined their association with glucose metabolism lipid metabolism an atherogenic lipid profile and inflammatory markers in 502 nondiabetic subjects A subgroup participated in a longitudinal study these subjects received diet counselling and increased their physical activityWe identified six variants of ADIPOR1 and seven variants of ADIPOR2 A singlenucleotide polymorphism SNP in the putative promoter region 8503 bp upstream of the translational start codon −8503 G/A of ADIPOR1 frequency of allele A=031 was in almost complete linkage disequilibrium with another SNP −1927 T/C in intron 1 Subjects carrying the −8503 A and −1927 C alleles had lower insulin sensitivity as estimated from a 75 g OGTT p=004 and determined during a euglycaemic clamp n=295 p=004 they also had higher HbA1c levels p=002 and although the difference was not statistically significant higher liver fat n=85 determined by proton magnetic resonance spectroscopy p=0056 all p values are adjusted for age sex and percentage of body fat In the longitudinal study n=45 the −8503 A and −1927 C alleles were associated with lower insulin sensitivity p=003 and higher liver fat p=002 at followup compared with the −8503 G and −1927 T alleles independently of basal measurements sex and baseline and followup percentage of body fat
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