Effect of SDF-1 and CXCR4 gene variants on the development of diabetic kidney disease

Diabetic kidney disease (DKD) is the gradual loss of renal function occurring in patients with diabetes. Stromal cell-derived factor-1 (SDF-1, encoded by <i>SDF-1</i> gene) is a chemokine that binds to its receptor, CXCR4, to mediate many aspects of renal biology. To test the potential impact of <i>SDF-1/CXCR4</i> gene variations on the risk for DKD, single-nucleotide polymorphisms (SNPs) of <i>SDF-1/CXCR4</i> genes were genotyped in 388 DKD patients and 335 DKD-free diabetic controls. Among 6 SNPs examined, we demonstrated that rs1801157 of <i>SDF-1</i> gene was associated with an increased risk for DKD (GA vs GG, AOR=2.252, <i>p</i>=0.035; GA+AA vs GG, AOR=2.156, <i>p</i>=0.036). Further stratification revealed that the correlation of rs1801157 with DKD was particularly detected in diabetic patients with early CKD but not in those with severe renal impairment. Instead, another SNP of <i>SDF-1</i> gene, rs266085, was found in association with the advanced form of DKD (TC vs TT, AOR=2.106, <i>p</i>=0.027; TC+CC vs TT, AOR=2.130, <i>p</i>=0.019), indicating differential impacts of <i>SDF-1</i> gene polymorphisms on the progressive loss of renal function in diabetic patients. Moreover, preliminary survey of public gene expression datasets showed that rs1801157 and rs266085 modulated <i>SDF-1</i> expression in many human tissues, and SDF-1/CXCR4 levels were elevated in renal tissues of DKD patients. These data suggest that allele-specific expression of <i>SDF-1</i> gene may influence DKD progression.