The association of SNP276G>T at adiponectin gene with circulating adiponectin and insulin resistance in response to mild weight loss.

ABSTRACT

OBJECTIVE: The purpose of this study was to determine whether common single nucleotide polymorphisms (SNPs) at the adiponectin (ADIPOQ) locus influence changes in circulating adiponectin and the features of insulin resistance in response to a weight loss intervention. SUBJECTS: In total, 294 nondiabetic/overweight-obese Koreans participated in a clinical intervention study lasting 12 weeks involving a caloric reduction of -300kcal/day. METHODS: Plasma adiponectin, blood lipids, glucose and insulin concentrations were measured at baseline and after weight loss. Insulin resistance was estimated by homeostasis model assessment insulin resistance (HOMA-IR) derived from fasting glucose and insulin concentrations. We genotyped for three SNPs, 45T>G, 276G>T and -11377C>G. RESULTS: At baseline, HOMA-IR was significantly higher in GG homozygotes than in carriers of the T allele at SNP276G>T of the adiponectin gene (P<0.05). With regard to SNP45T>G and SNP -11377C>G, we did not find any genotype related differences in baseline levels of HOMA-IR and adiponectin. In the 45/276 haplotype test, homozygous for the TG haplotype had significantly lower concentrations of plasma adiponectin (P<0.05). After the 12-week weight loss intervention, the significant decreases in HOMA-IR (P<0.001) and increases in adiponectin (P<0.01) were observed in GG homozygotes at SNP276, which were not shown in carriers of the T allele. Furthermore, there was a significant difference in the decreases in HOMA-IR between the GG homozygotes and carriers of the T allele at SNP276 (P<0.05). Regarding SNP45T>G and SNP -11377C>G, there was no association between SNP45T>G and SNP -11377C>G and decreases in HOMA-IR. In the 45/276 haplotype test, there was a significant difference in changes of adiponectin levels among those with different haplotype combinations (P<0.05). CONCLUSION: The SNP276G>T of the ADIPOQ gene is associated with different responses of circulating adiponectin and insulin resistance to mild weight loss in overweight-obese subjects.