Associations between glucose tolerance, insulin sensitivity and insulin secretion phenotypes and polymorphisms in adiponectin and adiponectin receptor genes in the Quebec Family Study

Aims Studies suggest that adiponectin (APM1) and its receptors 1 and 2 (AdipoR1 and AdipoR2) play an important role in the development of insulin resistance (IR). Our objective was to examine associations between APM1 (+45T > G, +276G > T and -3971A > G), AdipoR1 (-100G > T and -3882T > C) and AdipoR2 (-35361A > G and -1352G > A) genes single-nucleotide polymorphisms (SNPs) and adiponectin plasma levels, indicators of glucose tolerance, insulin sensitivity (IS) and insulin secretion. Methods Six hundred and twenty-two non-diabetic subjects from the Quebec Family Study (QFS) underwent a 75-g oral glucose tolerance test (OGTT), with measurement of fasting adiponectin, glucose, insulin and C-peptide levels. Indices of glucose tolerance, IS and insulin secretion were derived from fasting and OGTT measurements. Results Significant evidence of association was found between indices of IS and APM1 and AdipoR1 SNPs. The APM1 -3971G/G homozygotes exhibited a reduced area under the curve of insulin during the OGTT (P = 0.007) and higher Cederholm index (P = 0.01) compared to the A/A homozygotes. The APM1 +45T > G variant was also associated with fasting (P = 0.002) and 2-h (P = 0.007) glucose values as well as with higher Cederholm index (P = 0.04) and disposition index (P = 0.02). Finally, the AdipoR1 -3882T > C SNP was associated with fasting glucose (P = 0.03), the homeostasis model assessment for insulin resistance (P = 0.04) and an index of insulin secretion (P30/G30, P = 0.02). No evidence of association was found with plasma adiponectin levels. Conclusions These results provide evidence for an influence of common SNPs in the APM1 and AdipoR1 genes on different phenotypes of glucose and insulin metabolism associated with increased risk of type 2 diabetes.