An Analysis of Angiotensin Converting Enzyme Gene Polymorphisms and Non-Infectious Pulmonary Dysfunction after Hematopoietic Stem Cell Transplantation.

Non-infectious pulmonary dysfunction (NIPD) is a common but often fatal complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). An insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene has extensively been studied in relation to pulmonary fibrosis, and the D-allele frequency was reported to be significantly higher in patients with pulmonary fibrosis than in the control. We have previously found that increased D-allele frequency is also associated with NIPD after HSCT from HLA haplo-identical sibling donor. In this study, we performed a retrospective analysis to assess the relation between ACE I/D polymorphism and unrelated donor HSCT. 772 patients were enrolled in this study (461 males and 311 females, median age 23; range 0 to 52). The underlying diseases were 229 ALL, 188 ANLL, 168 CML, 66 MDS, 74 aplastic anemia, 24 lymphoma, 12 inherited disease and an other disease. DNA samples and clinical information were obtained from the Japan Marrow Donor Program registry. Determination of the ACE genotype was accomplished by polymerase chain reaction. NIPD occurred in 73 patients (9.5%). The D allele frequency and the D/D genotype frequency were not significantly different between the patients with NIPD and the patients without NIPD. However, the D/D genotype patients, whose donor also had D/D were frequently observed in the NIPD population (23.8% vs 9.1%; p = 0.05). Furthermore, an investigation of the relation between ACE genotype and onset of NIPD revealed that NIPD patients with the D/D genotype tended to be diagnosed faster than patients with the I/D or I/I (mean onset day 48.5, 95.2 and 110.6; p = 0.037). Our results suggest the involvement of ACE gene polymorphism in early onset NIPD, which may be different from late onset NIPD in respect to the pathogenesis.