International Journal of Hematology

DOI: 10.1007/s12185-019-02739-2 Pages: 112-119

Donor single nucleotide polymorphism in ACAT1 affects the incidence of graft-versus-host disease after bone marrow transplantation

1. Nagoya University Graduate School of Medicine, Department of Hematology and Oncology

2. Japanese Red Cross Nagoya First Hospital, Department of Hematology

Correspondence to:
Makoto Murata
Email: mmurata@med.nagoya-u.ac.jp

Close

Abstract

Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) is an enzyme that converts cholesterol to cholesteryl esters. A recent in vivo study reported that inhibiting ACAT1 enzyme activity upregulates the membrane cholesterol levels of T cells, enhancing their cytotoxic function. In the present study, we investigated whether the presence of the ACAT1 single nucleotide polymorphism rs11545566 in transplant donors affected the risk of graft-versus-host disease (GVHD) in 116 adult patients who underwent bone marrow transplantation from human leukocyte antigen-identical sibling donors, and who received GVHD prophylaxis with short-term methotrexate and cyclosporine. The frequencies of the AA, AG, and GG genotypes in the donors were 31%, 45%, and 24%, respectively. The cumulative incidences of grade II–IV acute GVHD on day 100 in patients whose donors had AA vs. non-AA genotypes were 6% and 18%, respectively, and those of extensive chronic GVHD at 2 years were 7% and 32%, respectively. Multivariate analyses demonstrated that donor rs11545566 non-AA genotypes showed a trend toward a higher incidence of grade II–IV acute GVHD (P = 0.079), and were significantly associated with a higher incidence of extensive chronic GVHD (P = 0.021). These results suggest that donor ACAT1 rs11545566 genotype may be predictive of GVHD.

To access the full text, please Sign in

If you have institutional access, please click here

Share the Knowledge