Role of the Functional Toll-Like Receptor-9 Promoter Polymorphism (-1237T/C) in Increased Risk of End-Stage Renal Disease: A Case-Control Study

Hsin Yi Yang, Kuo Cheng Lu, Herng Sheng Lee, Shih Ming Huang, Yuh Feng Lin, Chia Chao Wu, Donald M. Salter, Sui Lung Su

研究成果: 雜誌貢獻文章

9 引文 斯高帕斯(Scopus)

摘要

Inflammation induced by infectious and noninfectious triggers in the kidney may lead to end stage renal disease (ESRD). Toll-like receptor 9 (TLR-9) a receptor for CpG DNA is involved in activation of immune cells in renal disease and may contribute to chronic inflammatory disease progression through an interleukin-6 (IL-6) dependent pathway. Previous studies indicate that -1237T/C confers regulatory effects on TLR-9 transcription. To date the effect of TLR-9 polymorphisms on ESRD remains unknown. We performed a case-control study and genotyped 630 ESRD patients and 415 controls for -1237T/C, -1486T/C and 1635G/A by real-time PCR assays and assessed plasma concentration of IL-6 by ELISA. Haplotype association analysis was performed using the Haploview package. A luciferase reporter assay and real-time PCR were used to test the function of the -1237T/C promoter polymorphism. A significant association between -1237T/C in TLR-9 and ESRD was identified. The TCA, TTA and CCA haplotype of TLR-9 were associated with ESRD. ESRD patients carrying -1237TC had a higher mean plasma IL-6 level when compared with -1237TT. The TLR-9 transcriptional activity of the variant -1237CC allele is higher than the -1237TT allele. The results indicate that in a Han Chinese population the presence of the C allele of -1237T/C in the TLR-9 gene increases susceptibility towards development of ESRD. In vitro studies demonstrate that -1237T/C may be involved in the development of ESRD through transcriptional modulation of TLR-9.

原文英語
文章編號e58444
期刊PLoS One
8
發行號3
DOIs
出版狀態已發佈 - 三月 5 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

指紋 深入研究「Role of the Functional Toll-Like Receptor-9 Promoter Polymorphism (-1237T/C) in Increased Risk of End-Stage Renal Disease: A Case-Control Study」主題。共同形成了獨特的指紋。

  • 引用此