PMID- 12682890
OWN - NLM
STAT- MEDLINE
DCOM- 20031126
LR  - 20081121
IS  - 1527-6465 (Print)
IS  - 1527-6465 (Linking)
VI  - 9
IP  - 4
DP  - 2003 Apr
TI  - Tumor necrosis factor-alpha promoter polymorphisms and the risk of rejection 
      after liver transplantation: a case control analysis of 210 donor-recipient 
      pairs.
PG  - 377-82
AB  - After orthotopic liver transplantation (OLT), allograft rejection remains an 
      important problem and is the major reason that immunosuppressive therapy must be 
      administered. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory 
      mediator that is central to the immune response, and intragraft expression of 
      this cytokine is increased during acute cellular rejection (ACR). Polymorphisms 
      within the TNF promoter have been identified and correlated with alterations in 
      production. The aims of this study were to determine if an individual patient's 
      propensity to develop ACR is related to the presence of these genetic 
      polymorphisms (either alone or in combination) within donor and recipient tissue 
      and to determine if these polymorphisms affect patient survival after OLT. The 
      study group consisted of 210 patients who underwent OLT between 1989 and 1999 
      with at least 6 months survival, including 42 cases who had evidence of acute 
      cellular rejection (biopsy-proven, elevated enzymes, and response to increased 
      immunosuppression) and were matched 4:1 to controls (n = 168) with similar age, 
      gender, underlying liver disease, date of transplant, and baseline 
      immunosuppression. The underlying liver diseases were hepatisis C virus 
      (HCV)/alcohol (70), HCV alone (50), alcohol (30), primary biliary cirrhosis (15), 
      primary sclerosing cholangitis (15), autoimmune hepatitis/cirrhosis (10), 
      cryptogenic (15), and hepatitis B virus (HBV) (5). DNA was extracted from 
      paraffin-embedded donor and recipient liver tissue (total 420 samples), 
      amplified, and sequenced for TNF single-nucleotide polymorphisms (TNFA-308 A/G 
      and TNFA-238 A/G). We found no differences between the TNF allelic distributions 
      among donors without liver disease (presumably representative of a normal control 
      population) and patients with end-stage liver disease undergoing OLT. 
      Multivariate analysis revealed no association with TNF polymorphisms (within 
      donor or recipient tissue) and rejection risk or patient survival after 
      transplantation. In this large case control analysis of patients undergoing liver 
      transplantation for diverse etiologies, TNF promoter polymorphisms were not 
      independently associated with rejection or survival.
FAU - Jazrawi, Saad F
AU  - Jazrawi SF
AD  - Liver Transplantation Program, the Division of Gastroenterology/Hepatology, 
      Portland Veterans Administration Medical Center, OR 97207, USA.
FAU - Zaman, Atif
AU  - Zaman A
FAU - Muhammad, Zafaruddin
AU  - Muhammad Z
FAU - Rabkin, John M
AU  - Rabkin JM
FAU - Corless, Christopher L
AU  - Corless CL
FAU - Olyaei, Ali
AU  - Olyaei A
FAU - Biggs, Amy
AU  - Biggs A
FAU - Ham, John
AU  - Ham J
FAU - Chou, Sunwen
AU  - Chou S
FAU - Rosen, Hugo R
AU  - Rosen HR
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Liver Transpl
JT  - Liver transplantation : official publication of the American Association for the 
      Study of Liver Diseases and the International Liver Transplantation Society
JID - 100909185
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Case-Control Studies
MH  - Female
MH  - Gene Frequency
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Graft Rejection/*genetics
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Liver Failure/genetics/surgery
MH  - *Liver Transplantation
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Promoter Regions, Genetic/*genetics
MH  - Survival Analysis
MH  - Tissue Donors
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2003/04/19 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/04/19 05:00
PHST- 2003/04/19 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/04/19 05:00 [entrez]
AID - S1527646503000273 [pii]
AID - 10.1053/jlts.2003.50064 [doi]
PST - ppublish
SO  - Liver Transpl. 2003 Apr;9(4):377-82. doi: 10.1053/jlts.2003.50064.