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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numbere58444
JournalPLoS One
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 5 2013

Fingerprint

Toll-Like Receptor 9
kidney diseases
case-control studies
Polymorphism
Chronic Kidney Failure
Case-Control Studies
promoter regions
genetic polymorphism
interleukin-6
Interleukin-6
Alleles
Haplotypes
alleles
Real-Time Polymerase Chain Reaction
haplotypes
quantitative polymerase chain reaction
Assays
Kidney
Toll-like receptor 9
Association reactions

ASJC Scopus subject areas

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

Cite this

Role of the Functional Toll-Like Receptor-9 Promoter Polymorphism (-1237T/C) in Increased Risk of End-Stage Renal Disease : A Case-Control Study. / Yang, Hsin Yi; Lu, Kuo Cheng; Lee, Herng Sheng; Huang, Shih Ming; Lin, Yuh Feng; Wu, Chia Chao; Salter, Donald M.; Su, Sui Lung.

In: PLoS One, Vol. 8, No. 3, e58444, 05.03.2013.

Research output: Contribution to journalArticle

Yang, Hsin Yi ; Lu, Kuo Cheng ; Lee, Herng Sheng ; Huang, Shih Ming ; Lin, Yuh Feng ; Wu, Chia Chao ; Salter, Donald M. ; Su, Sui Lung. / Role of the Functional Toll-Like Receptor-9 Promoter Polymorphism (-1237T/C) in Increased Risk of End-Stage Renal Disease : A Case-Control Study. In: PLoS One. 2013 ; Vol. 8, No. 3.
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