title: 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.
authors: Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, Taipei, Taiwan, ROC.
authors: Kuo-Cheng
authors: KC
authors: Lu
authors: Hsin-Yi
authors: HY
authors: Yang
authors: Yuh-Feng
authors: YF
authors: Lin
authors: Sen-Yeong
authors: SY
authors: Kao
authors: Ching-Huang
authors: CH
authors: Lai
authors: Chi-Ming
authors: CM
authors: Chu
authors: Chia-Chao
authors: CC
authors: Wu
authors: Sui-Lung
authors: SL
authors: Su
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9