TY - JOUR
T1 - Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT
AU - Murase, M.
AU - Nishida, T.
AU - Onizuka, M.
AU - Inamoto, Y.
AU - Sugimoto, K.
AU - Imahashi, N.
AU - Murata, M.
AU - Miyamura, K.
AU - Kodera, Y.
AU - Inoko, H.
AU - Naoe, T.
PY - 2011/11
Y1 - 2011/11
N2 - 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=.040) and a trend toward higher OS (HR: 0.61, 95% CI: 0.36-1.0, P=.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.
AB - 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=.040) and a trend toward higher OS (HR: 0.61, 95% CI: 0.36-1.0, P=.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.
UR - http://www.scopus.com/inward/record.url?scp=80855164631&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80855164631&partnerID=8YFLogxK
U2 - 10.1038/bmt.2010.319
DO - 10.1038/bmt.2010.319
M3 - Article
C2 - 21170090
AN - SCOPUS:80855164631
SN - 0268-3369
VL - 46
SP - 1444
EP - 1449
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 11
ER -