Impact of polymorphisms of TLR4/CD14 and TLR3 on acute rejection in kidney transplantation

Young Hwan Hwang, Han Ro, Inho Choi, Hyunsook Kim, Kook Hwan Oh, Jong-Ik Hwang, Myoung Hee Park, Suhnggwon Kim, Jaeseok Yang, Curie Ahn

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background. Organ transplantation itself inevitably activates the innate immune system by toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the possible association between the TLR4/CD14 and TLR3 polymorphisms of donor-recipient pairs, and acute rejection after living donor kidney transplantation. Methods. TLR4 -1607T/C (rs10759932), -2026A/G (rs1927914); CDU -159C/T (rs2569190);and TLR3 rs3775290, rs3775291, and rs3775296 were genotyped using DNA samples from 216 donor-recipient pairs of adult living donor kidney transplantation between January 1996 and July 2006. Dual luciferase reporter assay was performed to determine the functional significance of promoter single-nucleotide polymorphisms (SNPs) of TLR4. Results. Acute rejection occurred in 42 recipients (19.4%) of 216 adult transplant patients within 1 year. The genotype distributions of both recipient and donor TLR4 rs10759932 differed significantly between the control (no rejection) and acute rejection groups. For recipient rs10759932, the adjusted odds ratio for the TC+CC over TT genotype was 0.25 (95% confidence interval, 0.11-0.57; P=0.001 ). When the rs10759932 CC genotype was present in the recipient or donor, no episode of acute rejection occurred (Fisher's exact test, P=0.023). The presence of the rs10759932 C allele was associated with higher rejection-free survival rates (log-rank test, P=0.0053). However, there was no difference in transcriptional activity between wild-type and variant promoters of TLR4. In contrast to TLR4, SNPs of TLR3 or CD14 had no influence on acute rejection. Conclusion. These findings suggest the importance of TLR4 in the pathogenesis of acute rejection in. kidney transplantation.

Original languageEnglish
Pages (from-to)699-705
Number of pages7
JournalTransplantation
Volume88
Issue number5
DOIs
Publication statusPublished - 2009 Sep 15

Fingerprint

Kidney Transplantation
Tissue Donors
Living Donors
Genotype
Single Nucleotide Polymorphism
Toll-Like Receptors
Graft Rejection
Organ Transplantation
Luciferases
Allografts
Immune System
Survival Rate
Alleles
Odds Ratio
Confidence Intervals
Transplants
DNA

Keywords

  • Acute rejection
  • Kidney transplantation
  • Polymorphism
  • Toll-like receptor

ASJC Scopus subject areas

  • Transplantation

Cite this

Impact of polymorphisms of TLR4/CD14 and TLR3 on acute rejection in kidney transplantation. / Hwang, Young Hwan; Ro, Han; Choi, Inho; Kim, Hyunsook; Oh, Kook Hwan; Hwang, Jong-Ik; Park, Myoung Hee; Kim, Suhnggwon; Yang, Jaeseok; Ahn, Curie.

In: Transplantation, Vol. 88, No. 5, 15.09.2009, p. 699-705.

Research output: Contribution to journalArticle

Hwang, YH, Ro, H, Choi, I, Kim, H, Oh, KH, Hwang, J-I, Park, MH, Kim, S, Yang, J & Ahn, C 2009, 'Impact of polymorphisms of TLR4/CD14 and TLR3 on acute rejection in kidney transplantation', Transplantation, vol. 88, no. 5, pp. 699-705. https://doi.org/10.1097/TP.0b013e3181b2f34a
Hwang, Young Hwan ; Ro, Han ; Choi, Inho ; Kim, Hyunsook ; Oh, Kook Hwan ; Hwang, Jong-Ik ; Park, Myoung Hee ; Kim, Suhnggwon ; Yang, Jaeseok ; Ahn, Curie. / Impact of polymorphisms of TLR4/CD14 and TLR3 on acute rejection in kidney transplantation. In: Transplantation. 2009 ; Vol. 88, No. 5. pp. 699-705.
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abstract = "Background. Organ transplantation itself inevitably activates the innate immune system by toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the possible association between the TLR4/CD14 and TLR3 polymorphisms of donor-recipient pairs, and acute rejection after living donor kidney transplantation. Methods. TLR4 -1607T/C (rs10759932), -2026A/G (rs1927914); CDU -159C/T (rs2569190);and TLR3 rs3775290, rs3775291, and rs3775296 were genotyped using DNA samples from 216 donor-recipient pairs of adult living donor kidney transplantation between January 1996 and July 2006. Dual luciferase reporter assay was performed to determine the functional significance of promoter single-nucleotide polymorphisms (SNPs) of TLR4. Results. Acute rejection occurred in 42 recipients (19.4{\%}) of 216 adult transplant patients within 1 year. The genotype distributions of both recipient and donor TLR4 rs10759932 differed significantly between the control (no rejection) and acute rejection groups. For recipient rs10759932, the adjusted odds ratio for the TC+CC over TT genotype was 0.25 (95{\%} confidence interval, 0.11-0.57; P=0.001 ). When the rs10759932 CC genotype was present in the recipient or donor, no episode of acute rejection occurred (Fisher's exact test, P=0.023). The presence of the rs10759932 C allele was associated with higher rejection-free survival rates (log-rank test, P=0.0053). However, there was no difference in transcriptional activity between wild-type and variant promoters of TLR4. In contrast to TLR4, SNPs of TLR3 or CD14 had no influence on acute rejection. Conclusion. These findings suggest the importance of TLR4 in the pathogenesis of acute rejection in. kidney transplantation.",
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T1 - Impact of polymorphisms of TLR4/CD14 and TLR3 on acute rejection in kidney transplantation

AU - Hwang, Young Hwan

AU - Ro, Han

AU - Choi, Inho

AU - Kim, Hyunsook

AU - Oh, Kook Hwan

AU - Hwang, Jong-Ik

AU - Park, Myoung Hee

AU - Kim, Suhnggwon

AU - Yang, Jaeseok

AU - Ahn, Curie

PY - 2009/9/15

Y1 - 2009/9/15

N2 - Background. Organ transplantation itself inevitably activates the innate immune system by toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the possible association between the TLR4/CD14 and TLR3 polymorphisms of donor-recipient pairs, and acute rejection after living donor kidney transplantation. Methods. TLR4 -1607T/C (rs10759932), -2026A/G (rs1927914); CDU -159C/T (rs2569190);and TLR3 rs3775290, rs3775291, and rs3775296 were genotyped using DNA samples from 216 donor-recipient pairs of adult living donor kidney transplantation between January 1996 and July 2006. Dual luciferase reporter assay was performed to determine the functional significance of promoter single-nucleotide polymorphisms (SNPs) of TLR4. Results. Acute rejection occurred in 42 recipients (19.4%) of 216 adult transplant patients within 1 year. The genotype distributions of both recipient and donor TLR4 rs10759932 differed significantly between the control (no rejection) and acute rejection groups. For recipient rs10759932, the adjusted odds ratio for the TC+CC over TT genotype was 0.25 (95% confidence interval, 0.11-0.57; P=0.001 ). When the rs10759932 CC genotype was present in the recipient or donor, no episode of acute rejection occurred (Fisher's exact test, P=0.023). The presence of the rs10759932 C allele was associated with higher rejection-free survival rates (log-rank test, P=0.0053). However, there was no difference in transcriptional activity between wild-type and variant promoters of TLR4. In contrast to TLR4, SNPs of TLR3 or CD14 had no influence on acute rejection. Conclusion. These findings suggest the importance of TLR4 in the pathogenesis of acute rejection in. kidney transplantation.

AB - Background. Organ transplantation itself inevitably activates the innate immune system by toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the possible association between the TLR4/CD14 and TLR3 polymorphisms of donor-recipient pairs, and acute rejection after living donor kidney transplantation. Methods. TLR4 -1607T/C (rs10759932), -2026A/G (rs1927914); CDU -159C/T (rs2569190);and TLR3 rs3775290, rs3775291, and rs3775296 were genotyped using DNA samples from 216 donor-recipient pairs of adult living donor kidney transplantation between January 1996 and July 2006. Dual luciferase reporter assay was performed to determine the functional significance of promoter single-nucleotide polymorphisms (SNPs) of TLR4. Results. Acute rejection occurred in 42 recipients (19.4%) of 216 adult transplant patients within 1 year. The genotype distributions of both recipient and donor TLR4 rs10759932 differed significantly between the control (no rejection) and acute rejection groups. For recipient rs10759932, the adjusted odds ratio for the TC+CC over TT genotype was 0.25 (95% confidence interval, 0.11-0.57; P=0.001 ). When the rs10759932 CC genotype was present in the recipient or donor, no episode of acute rejection occurred (Fisher's exact test, P=0.023). The presence of the rs10759932 C allele was associated with higher rejection-free survival rates (log-rank test, P=0.0053). However, there was no difference in transcriptional activity between wild-type and variant promoters of TLR4. In contrast to TLR4, SNPs of TLR3 or CD14 had no influence on acute rejection. Conclusion. These findings suggest the importance of TLR4 in the pathogenesis of acute rejection in. kidney transplantation.

KW - Acute rejection

KW - Kidney transplantation

KW - Polymorphism

KW - Toll-like receptor

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