PMID- 11744409
OWN - NLM
STAT- MEDLINE
DCOM- 20020318
LR  - 20190921
IS  - 1053-2498 (Print)
IS  - 1053-2498 (Linking)
VI  - 20
IP  - 12
DP  - 2001 Dec
TI  - Influence of tumor necrosis factor-alpha gene-308 polymorphism on the development 
      of coronary vasculopathy after cardiac transplantation.
PG  - 1265-73
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been implicated in 
      cardiovascular disease. Polymorphism of the TNF-alpha gene promoter region 
      (position -308) influences an individual's production of TNF-alpha. This affects 
      susceptibility to acute rejection after cardiac transplantation. Because the 
      highest serum levels of TNF-alpha have been found in recipients with cardiac 
      transplant vasculopathy and because TNF-alpha blockade can prevent the disease in 
      rabbits, we investigated the effect of TNF-alpha promoter polymorphism on the 
      development of vasculopathy in human cardiac allograft recipients. METHODS: Using 
      sequence-specific primers to the TNF-alpha gene and polymerase chain reaction, 
      the genotypes of 147 cardiac transplant recipients and 134 heart donors were 
      identified. An association was sought between the presence of high-producing (A 
      homozygotes, GA heterozygotes) or low-producing (G homozygotes) TNF-alpha 
      genotype and the development of coronary vasculopathy, diagnosed by routine 
      surveillance coronary angiography. RESULTS: We found that 31.9% of recipients and 
      27.0% of donors were high TNF-alpha producers. The presence of the high-producing 
      TNF-alpha allele led to an earlier diagnosis of vasculopathy; 3.42 years (+/- 
      91.3 days) vs 3.84 years (+/- 76.3 days) for high- and low-producing cardiac 
      graft recipients, respectively; 3.52 years (+/- 87.3 days) vs 3.78 years (+/- 
      77.4 days) for high- and low-producing donor grafts, respectively. However, 
      neither of these differences were significant. By Kaplan Meier actuarial analysis 
      and log-rank test, TNF-alpha polymorphism had no effect on the freedom from 
      vasculopathy when considering either recipient (p = 0.99) or donor (p = 0.86) 
      TNF-alpha genotype. Multivariate analysis identified increasing donor age and the 
      number of acute rejection episodes of International Society for Heart and Lung 
      Transplantation grade 3 or greater as independent risk factors for vasculopathy 
      in both the recipient and donor cohorts. CONCLUSIONS: Polymorphism at position 
      -308 in the promoter region of the TNF-alpha gene fails to predict the 
      development of cardiac transplant-related vasculopathy and cannot be used as a 
      genetic risk marker. This may be because of the effects of immunosuppressive 
      treatment.
FAU - Densem, C G
AU  - Densem CG
AD  - Cardiothoracic Transplant Unit, Wythenshawe Hospital, United Kingdom, Manchester, 
      UK.
FAU - Hutchinson, I V
AU  - Hutchinson IV
FAU - Yonan, N
AU  - Yonan N
FAU - Brooks, N H
AU  - Brooks NH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Coronary Artery Disease/*genetics/pathology
MH  - Coronary Vessels/pathology
MH  - Female
MH  - *Genotype
MH  - Graft Rejection/*genetics/pathology
MH  - Heart Transplantation/*pathology
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Genetic/*genetics
MH  - Promoter Regions, Genetic/*genetics
MH  - Tissue Donors
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2001/12/18 10:00
MHDA- 2002/03/19 10:01
CRDT- 2001/12/18 10:00
PHST- 2001/12/18 10:00 [pubmed]
PHST- 2002/03/19 10:01 [medline]
PHST- 2001/12/18 10:00 [entrez]
AID - S1053249801003588 [pii]
AID - 10.1016/s1053-2498(01)00358-8 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2001 Dec;20(12):1265-73. doi: 
      10.1016/s1053-2498(01)00358-8.