title: ACE deletion polymorphism is associated with a high risk of non-infectious pulmonary complications after stem cell transplantation.
abstract: Non-infectious pulmonary complication (NIPC) is a serious adverse event for allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. NIPC includes both categories of lung complications: early onset idiopathic pneumonia syndrome (IPS) (onset <120 days) and late-onset non-infectious pulmonary complications (LONIPCs). Both categories have high mortality and morbidity rates, and critical treatments are not available. The renin-angiotensin system plays a critical role in pulmonary fibrosis. We, therefore, studied the relationship between angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphisms and NIPC incidence in 149 consecutive allo-HSCT recipients. A total of 12.1 % (18/149) of these patients were diagnosed with NIPC (IPS, 3; LONIPCs, 15). Eight NIPC patients died from respiratory failure (mortality rate, 44.4 %). Peripheral blood stem cell transplantation was associated with a significantly higher incidence of NIPC than bone marrow transplantation and cord blood transplantation by univariate analysis (HR 3.13, P = 0.031). The serum ACE levels differed significantly according to the ACE insertion/deletion polymorphism. Patients with an ACE D/D genotype occurred at a significantly higher frequency among NIPC patients than I/D and I/I patients (HR 9.03, P < 0.0001). Multivariate analysis confirmed that NIPC is associated with ACE D/D genotypes (HR 8.8, P < 0.001). Our data support a role for the renin-angiotensin system in the pathogenesis of NIPC after allo-HSCT, and may represent a therapeutic target for complications.
authors.affiliation: Department of Hematology and Oncology, Tokai University School of Medicine, 143 shimokasuya, Isehara, Kanagawa, 259-1143, Japan.
authors.forename: Mitsuki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Onizuka
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Machida
authors.forename: Masako
authors.initials: M
authors.lastname: Toyosaki
authors.forename: Jun
authors.initials: J
authors.lastname: Amaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Kawai
authors.forename: Ai
authors.initials: A
authors.lastname: Sato
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawada
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006785:Hospitals, University; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008171:Lung Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors; D055815:Young Adult
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A