Glucose transporter (GLUT1) allele (XbaI-) associated with nephropathy in non-insulin-dependent diabetes mellitus.

Abstract

Although multiple factors contribute to the initiation and progression of diabetic nephropathy (DN), hyperglycemia and genetic predisposition are two major components implicated in the development of DN. Several pieces of experimental evidence suggest that glucose transporter (GLUT1) activity is an important modulator for the cell hypertrophy and extracellular matrix formation of glomerular mesangial cells. To evaluate the role of the GLUT1 gene mutation in the development of DN in Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM), the polymorphic XbaI site of GLUT1 gene was analyzed by polymerase chain reaction in 124 normal subjects and 131 patients with NIDDM, among whom 64 were complicated with DN. DN was defined as persistent albuminuria with or without impaired renal function with no known cause of renal disease other than diabetes. The frequencies of XbaI (+/-) genotype (75 vs. 44%, P < 0.01) and XbaI (-) allele (44 vs. 29%, P < 0.05) were significantly higher in NIDDM patients with DN than those without nephropathy. There were no significant differences for GLUT1 genotype and allele frequency between NIDDM patients without nephropathy and normal subjects. The presence of the XbaI (-) allele appeared to have a strong association with the development of DN. The odds ratio was 1.915, and the 95% confidence interval was 1.044 to 3.514. In addition, no strong association was found between GLUT1 gene polymorphism and retinopathy in NIDDM patients. Our results indicate that the XbaI (-) allele of the GLUT1 gene might be a genetic marker of NIDDM with DN, and this genetic susceptibility is independent of its retinopathy in Chinese subjects.