Effect of the TNF-alpha-promoter polymorphism on cardiac allograft rejection.
BACKGROUND
A polymorphism exists in the tumor necrosis factor alpha (TNF-alpha) promoter (position -308, G/A = TNFA1/TNFA2). The TNFA2 allele is associated with increased TNF-alpha production in vitro and has been reported to increase the risk of allograft rejection in pediatric recipients of cardiac transplantation. We examined the effect of the TNFA2 allele on the risk of allograft rejection in adult cardiac transplant recipients.


METHODS
We prospectively analyzed 57 subjects (aged 54 +/- 11 years, 84% men, 49% ischemic) who underwent cardiac transplantation between October 1996 and July 2001. Patients were observed after transplantation (mean, 910 +/- 605 days) and the frequency of allograft rejection (biopsy Grade > or =2) in patients with the TNFA2 allele (Group A, n = 15) was compared with TNFA1 homozygotes (Group B, n = 42). Overall survival and time to rejection episodes also were compared between groups.


RESULTS
The frequency of allograft rejection was similar between groups (Group A, 8/15 [56%]; Group B, 22/42 [52%]; p = 0.77). Time to rejection also was comparable (Group A, 17 +/- 11 days; Group B, 20 +/- 20 days, p = 0.74). Overall post-transplant survival was similar between groups (1- and 2-year percentage survival: Group A, 87% and 78%, Group B, 88% and 82%, p = 0.35).


CONCLUSIONS
The TNFA2 allele was not associated with increased risk of rejection in adult cardiac transplant recipients. The impact of this polymorphism on overall post-transplant outcomes will require investigation in larger multicenter studies.
Bedi
Maninder
M
Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Postava
Lisa A
LA
Murali
Srinivas
S
MacGowan
Guy A
GA
Mathier
Michael
M
Shears
Lawrence
L
Kormos
Robert
R
Holubkov
Richard
R
London
Barry
B
McNamara
Dennis M
DM
D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha