Association of two glyoxalase I gene polymorphisms with nephropathy and retinopathy in Type 2 diabetes

Background: Glyoxalase I (GLO1), which is the major enzyme that catalyzes the metabolism of methylglyoxal (MG), may play an important role in the pathogenesis of diabetic microvascular complications. Aim: To investigate whether the C-7T and A419C polymorphisms of the GLO1 gene are associated with nephropathy and retinopathy in Chinese Type 2 diabetic patients. Subjects and methods: A total of 364 Type 2 diabetic patients and 301 healthy controls were enroled in the study. Diabetic microvascular complications were determined by urinary albumin excretion measurements and ophthalmological examinations. Genetic analyses were performed using either Taqman PCR or direct sequencing. The effect of C-7T polymorphism on promoter activity was measured by reporter gene assays. Results: The albumin/creatinine ratio (ACR) and prevalence of nephropathy and retinopathy were significantly higher in diabetic patients with GLO1 -7CC genotype than in patients with -7CT and -7TT genotypes (p=0.02, p=0.02, and p=0.04, respectively). The 7CC genotype is independently associated with ACR (β=0.13, p=0.01) and the risk for retinopathy [odds ratio (OR): 2.30, 95% confidence interval (CI): 1.25–4.24, p<0.01]. The luciferase activity of the -7T promoter was higher than that of the -7C promoter (13.2±0.2 vs 11.7±0.8, p=0.04). No differences were found between ACR and the prevalence of nephropathy and retinopathy for A419C polymorphism in Type 2 diabetic patients. Conclusions: GLO1 C-7T polymorphism alters promoter activity and confers susceptibility to nephropathy and retinopathy to Type 2 diabetic patients.