title: Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT.
abstract: CTLA-4 is a negative regulator of activated T cells and the association of CTLA-4 polymorphisms with autoimmune diseases and transplant outcome has been reported. We evaluated the effect of donor CTLA-4 polymorphisms on outcome after allogeneic hematopoietic SCT (HSCT). We analyzed 147 Japanese HLA-matched sibling recipients and their donors who had undergone allogeneic HSCT. Genotyping of three single-nucleotide polymorphisms in CTLA-4 (-318, +49, CT60) was performed using TaqMan-PCR. According to the international HapMap database, only these three CTLA-4 haplotypes, classified as C-G-G, C-A-A and T-A-G, are present in the Japanese population. In this study, percentage expression of the C-G-G, C-A-A and T-A-G haplotypes was 59.5, 30.6 and 9.9%, respectively. Recipients of the C-A-A haplotype donor showed a significantly lower risk of relapse (HR: 0.54, 95% CI: 0.30-0.97, P=0.040) and a trend toward higher OS (HR: 0.61, 95% CI: 0.36-1.0, P=0.054) than did recipients of a donor without the C-A-A haplotype. The presence or absence of the C-A-A haplotype did not affect GVHD or non-relapse mortality. As the presence of the C-A-A haplotype reduced relapse risk and improved survival after allogeneic HSCT, this CTLA-4 haplotype may provide useful information for donor selection.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murase
authors.forename: T
authors.initials: T
authors.lastname: Nishida
authors.forename: M
authors.initials: M
authors.lastname: Onizuka
authors.forename: Y
authors.initials: Y
authors.lastname: Inamoto
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.forename: N
authors.initials: N
authors.lastname: Imahashi
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: K
authors.initials: K
authors.lastname: Miyamura
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
authors.forename: H
authors.initials: H
authors.lastname: Inoko
authors.forename: T
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D060908:CTLA-4 Antigen / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006086:Graft vs Host Disease / Q000517:prevention & control; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D035781:Siblings; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D060908:CTLA-4 Antigen