The T-1237C Polymorphism of the Toll-like Receptor-9 Gene Is Associated with Chronic Kidney Disease in a Han Chinese Population

Abstract

Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. As inflammatory processes and genetic factors are involved in the pathogenesis of CKD, we have investigated the potential genetic contribution of Toll-like receptor (TLR) gene polymorphisms in CKD. In a case-control association study, 149 CKD patients and 429 healthy controls were genotyped by real-time polymerase chain reaction. CKD patients were defined as kidney damage (albuminuria, proteinuria or hematuria) or glomerular filtration rate < 60 ml/min/1.73 m(2) for 3 months or more. Single nucleotide polymorphisms (SNPs) at TLR-2 G2408A, TLR-4 A12874G and C13174T, and TLR-9 T-1237C, T-1486C, and G1635A were assessed, and linkage disequilibrium calculations and haplotype association analysis were undertaken. The functions of TLR-9 have been documented to recognize the viral and bacterial CpG DNA sequences, whereas detects microbe-derived peptidoglycan and lipopeptides and TLR-4 binds lipopolysaccharides. SNPs within the TLR genes may influence promoter activity, mRNA conformation and subcellular localization, and/or protein structure and function. Our results show that only the TLR-9 T-1237C and G1635A gene polymorphisms demonstrate an association with CKD (p = 0.002 and p = 0.04, respectively). The TLR-9 TCA haplotype at T-1237C, T-1486C, and G1635A was associated with a lower risk of CKD, whereas the TTA haplotype was associated with a higher risk of CKD. In the Han Chinese population, those who carry the C and A alleles at SNPs T-1237C and G1635A in the TLR-9 gene appear to be more susceptible to the development of CKD.