Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome

Background: Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. Aim: The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. Methods: We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. Results: We identified three AdipoR2 variants (+795G/ A, +870C/A and +963C/T) in perfect linkage disequilibrium (r(2) = 1) with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. Conclusion: To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism.