Association between heme oxygenase-1 gene promoter polymorphisms and type 2 diabetes in a Chinese population

Abstract

The authors aimed to determine whether 2 functional polymorphisms in the heme oxygenase-1 (HO-1) gene promoter are associated with type 2 diabetes mellitus (T2DM). A Chinese case-control study involving 1,103 newly diagnosed T2DM patients, 371 patients with impaired glucose regulation (IGR), and 1,615 controls was performed (December 2004-December 2007). A (GT)n microsatellite polymorphism and a single nucleotide polymorphism, T(-413)A, were genotyped, and their functional relevance was evaluated by examining the level of HO-1 protein expression. For the (GT)n microsatellite polymorphism, genotypes with the L (GT)n allele (≥25 GT repeats) were associated with increased odds of IGR or T2DM compared with the S/S genotype (<25 GT repeats) (S/L genotype: odds ratio (OR)=1.35, P=0.048; L/L genotype: OR=1.65, P=0.006). Subsequent haplotype analysis showed that haplotype TL contributed to increased odds of IGR or T2DM compared with haplotype TS (OR=1.56, P=0.003). In functional analyses, HO-1 expression level was significantly reduced in persons with IGR and T2DM carrying the L/L (GT)n genotype compared with persons with the S/S genotype. Further haplotype combination assay confirmed the functional dominance of the (GT)n microsatellite polymorphism over the T(-413)A single nucleotide polymorphism. These results support an association between the HO-1 (GT)n microsatellite polymorphism, HO-1 expression levels, and the odds of T2DM.