BACKGROUND: The heme oxygenase-1 (HO-1) isoenzyme has recently been suggested to protect transplants from ischemia-reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study, we investigated the impact of the promoter polymorphism on the development of cardiac allograft vasculopathy (CAV) in human heart transplants. METHODS: We enrolled 152 recipients of a heart allograft with at least 1 year survival post-transplantation in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from paraffin-embedded allograft biopsy specimens. Patients were followed angiographically for CAV. Angiographic vessel-wall abnormalities were defined as CAV, and a stenosis of more than 50% in at least 1 vessel area was defined as severe CAV. RESULTS: Eighty-seven patients (57%) had received a heart from a donor with at least 1 class S allele. Within the mean follow-up period of 9 years, 95 patients (63%) showed signs of CAV, among which 60 patients (40%) developed severe CAV. The frequency of CAV and severe CAV was not significantly different between class S allele recipients and non-recipients (CAV, 57/87 vs 38/65, p = 0.12; severe CAV, 35/87 vs 25/65, p = 0.30). CONCLUSION: In contrast to recent findings in renal allografts and vascular injury, the HO-1 gene promoter polymorphism does not show an association with the development of CAV in heart transplants.
BACKGROUND: The heme oxygenase-1 (HO-1) isoenzyme has recently been suggested to protect transplants from ischemia-reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study, we investigated the impact of the promoter polymorphism on the development of cardiac allograft vasculopathy (CAV) in human heart transplants. METHODS: We enrolled 152 recipients of a heart allograft with at least 1 year survival post-transplantation in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from paraffin-embedded allograft biopsy specimens. Patients were followed angiographically for CAV. Angiographic vessel-wall abnormalities were defined as CAV, and a stenosis of more than 50% in at least 1 vessel area was defined as severe CAV. RESULTS: Eighty-seven patients (57%) had received a heart from a donor with at least 1 class S allele. Within the mean follow-up period of 9 years, 95 patients (63%) showed signs of CAV, among which 60 patients (40%) developed severe CAV. The frequency of CAV and severe CAV was not significantly different between class S allele recipients and non-recipients (CAV, 57/87 vs 38/65, p = 0.12; severe CAV, 35/87 vs 25/65, p = 0.30). CONCLUSION: In contrast to recent findings in renal allografts and vascular injury, the HO-1 gene promoter polymorphism does not show an association with the development of CAV in heart transplants.
Authors: Chau-Chyun Sheu; Rihong Zhai; Zhaoxi Wang; Michelle N Gong; Paula Tejera; Feng Chen; Li Su; B Taylor Thompson; David C Christiani Journal: Intensive Care Med Date: 2009-06-13 Impact factor: 17.440