Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: A 5-year follow-up study

Aims/hypothesis: Polymorphisms of the gene encoding adiponectin (ADIPOQ) have previously been associated with type 2 diabetes in Europid and Japanese subjects, but not in Pima Indians. The aim of this study was to determine the contribution made by ADIPOQ gene variants to glycaemic status in southern Chinese individuals. Subjects and methods: Sixty unrelated subjects were screened for single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene by direct sequencing. The association of tagging SNPs with the outcome of glycaemic status in 262 subjects with impaired glucose tolerance (IGT) was examined in a 5-year prospective study. Results: We identified 15 polymorphisms in the ADIPOQ gene, ten of them constituting the tagging SNPs. At 5 years, 39.7% of the subjects with IGT had regressed to NGT, 41.2% had persistent IGT or impaired fasting glucose and 19.1% had developed diabetes. Only the T45G polymorphism was associated with persistent hyperglycaemia at 5 years (p=0.001). Haplotypes formed by the addition of other SNPs, as haplotype blocks or pairs, did not confer greater association than T45G alone. On logistic regression analysis, T45G independently predicted persistent hyperglycaemia at 5 years (OR=2.25, 95% CI 1.29-3.95, G carriers vs TT; p=0.005). It also predicted persistent hyperglycaemia in a nested case-control study involving 158 sex- and age-matched controls with persistent NGT (p=0.012, adjusted for BMI), and that of diabetes or glycaemia progression (p<0.05) in a meta-analysis that also included two published studies in Europid subjects. Conclusions/interpretation: Our findings support a significant role of this common ADIPOQ gene polymorphism in predicting glycaemic status in southern Chinese people.