Effect of the TNF-α–promoter polymorphism on cardiac allograft rejection

Bedi, Maninder; Postava, Lisa A; Murali, Srinivas; MacGowan, Guy A; Mathier, Michael; Shears, Lawrence; Kormos, Robert; Holubkov, Richard; London, Barry; McNamara, Dennis M

doi:10.1016/j.healun.2003.07.012

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 23, Issue 6 , Pages 696-700, June 2004

Effect of the TNF-α–promoter polymorphism on cardiac allograft rejection☆

Maninder Bedi, MD
- Cardiovascular Institute , University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Lisa A Postava, MBA
- Cardiovascular Institute , University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Srinivas Murali, MD
- Cardiovascular Institute , University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Guy A MacGowan, MD
- Cardiovascular Institute , University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Michael Mathier, MD
- Cardiovascular Institute , University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Lawrence Shears, MD
- Division of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Robert Kormos, MD
- Division of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Richard Holubkov, PhD
- Department of Family and Preventive Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, USA
Barry London, MD, PhD
- Cardiovascular Institute , University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Dennis M McNamara, MD
- Cardiovascular Institute , University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
- Reprint requests: Dennis M. McNamara, MD, Heart Failure Section, University of Pittsburgh, 200 Lothrop Street, S-558 Scaife Hall, Pittsburgh, Pennsylvania 15213-2582, USA. Telephone: 412-647-2703. Fax: 412-647-0595.

Received 2 December 2002; received in revised form 20 June 2003; accepted 27 July 2003.

Abstract

Background

A polymorphism exists in the tumor necrosis factor α (TNF-α) promoter (position −308, G/A = TNFA1/TNFA2). The TNFA2 allele is associated with increased TNF-α 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 ≥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).

Conclusion

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.