Association between the GLUT1 gene polymorphism and the risk of diabetic nephropathy: a meta-analysis

The association between diabetic nephropathy (DN) and the XbalphaI polymorphism in the GLUT1 gene has been investigated in several case-control studies. These studies rendered contradictory results: the allele XbalphaI(-) was shown either to be a risk factor or neutral, or even protective for the development of the disease. To shed some light on these inconclusive findings, a meta-analysis of all available studies relating the XbalphaI polymorphism to the risk of developing DN was conducted. Five out of six identified studies included Caucasian populations, and only one involved samples from an Asian population. Overall, the meta-analysis suggested large heterogeneity between studies (P<0.01, I2=68%) and lack of association between allele XbalphaI(-) and the risk of developing DN relative to allele XbalphaI(+): random effects odds ratio (OR)=1.26 [95% CI (0.93, 1.69)]. Excluding one study with the controls not in Hardy-Weinberg equilibrium, the sensitivity analysis revealed that heterogeneity (P=0.28, I2=21%) could be explained, and then, there is an overall association: fixed effects OR=1.34 [95% CI (1.13, 1.60)]. Then, significant ORs were also found on analysis of subgroups: for the Caucasian population, fixed effects OR=1.29 [95% CI (1.08, 1.56)] and for the type 2 diabetic patients fixed effects OR=1.69 [95% CI (1.09, 2.63)]. In type 1 diabetes, there is a moderate heterogeneity (P=0.19, I2=41%) with fixed effects OR=1.29 [95% CI (1.06, 1.56)] and random effects OR=1.32 [95% CI (1.01, 1.71)]. There is a source of bias in the selected studies: large studies failed to show association while small studies claimed an association. Although there is evidence of association between GLUT1 and DN, the above findings reinforce the need for further and more rigorous association studies.