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Donor polymorphisms of toll-like receptor 4 associated with graft failure in liver transplant recipients.
- Source :
-
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society [Liver Transpl] 2012 Dec; Vol. 18 (12), pp. 1399-405. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 American Association for the Study of Liver Diseases.)
- Subjects :
- Adult
Black or African American genetics
Aged
Female
Graft Survival immunology
Hepatitis C complications
Humans
Linear Models
Liver Transplantation ethnology
Liver Transplantation immunology
Male
Middle Aged
Multivariate Analysis
Proportional Hazards Models
Risk Assessment
Risk Factors
Treatment Outcome
White People genetics
Young Adult
Graft Survival genetics
Liver Transplantation adverse effects
Polymorphism, Single Nucleotide
Tissue Donors
Toll-Like Receptor 4 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1527-6473
- Volume :
- 18
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
- Publication Type :
- Academic Journal
- Accession number :
- 22987288
- Full Text :
- https://doi.org/10.1002/lt.23549