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. 2012 Dec;18(12):1399-405.
doi: 10.1002/lt.23549.

Donor polymorphisms of toll-like receptor 4 associated with graft failure in liver transplant recipients

William S Oetting  1 , Weihua Guan, David P Schladt, Robert E Leduc, Pamala A Jacobson, Arthur J Matas, Srinath Chinnakotla, Bernd Schröppel, Barbara T Murphy, Ajay K Israni
Affiliations

Donor polymorphisms of toll-like receptor 4 associated with graft failure in liver transplant recipients

William S Oetting et al. Liver Transpl. 2012 Dec.

Abstract

There have been many reports showing significant associations between recipient genetic variants and allograft outcomes, including acute rejection and graft failure, but less is known about the contribution of the donor genotype. We analyzed 37 single-nucleotide polymorphisms (SNPs) within the toll-like receptor 4 (TLR4) gene from deceased donor liver allografts transplanted into 738 recipients to determine their effects on liver graft failure (LGF). Two SNPs exhibited a significant association with LGF after adjustments for donor race and recipient race and corrections for multiple test comparisons: rs11536865 [hazard ratio (HR) = 2.5, P = 0.0003] and rs5030717 (HR = 1.67, P = 0.0008). An additional SNP, rs913930, exhibited a significant association in Caucasian donors (HR = 1.62, P = 0.0006), and 2 SNPs exhibited a suggestive association in African American donors: rs11536865 (HR = 2.45, P = 0.002) and rs5030717 (HR = 2.32, P = 0.002). Additionally, the liver donor risk index (HR = 2.56, 95% confidence interval = 1.54-4.26, P = 0.0003) and the recipient hepatitis C virus (HCV) status (HR = 1.53, 95% confidence interval = 1.04-2.24, P = 0.032) increased the risk of all-cause LGF in a Cox proportional hazards model adjusted for recipient race. Donor polymorphisms in TLR4 could be important factors in modulating TLR4 activity and, therefore, affect the risk of graft loss. Additionally, there is a suggestion of an interaction between polymorphisms within TLR4 and the HCV status.

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Figures

Figure 1
Figure 1. Time to all-cause liver graft failure
Kaplan-Meyer curve showing the effect of rs913930 genotypes on graft survival in Caucasians only. 610 recipients received livers from Caucasian donors with 112 (18%) having liver graft failure.
See this image and copyright information in PMC

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