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

• Published in: International journal of hematology Vol. 111; no. 1; pp. 112 - 119
• Main Authors: Kamoshita, Sonoko, Murata, Makoto, Koyama, Daisuke, Julamanee, Jakrawadee, Okuno, Shingo, Takagi, Erina, Miyao, Kotaro, Goto, Tatsunori, Ozawa, Yukiyasu, Miyamura, Koichi, Terakura, Seitaro, Nishida, Tetsuya, Kiyoi, Hitoshi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.01.2020; Springer Nature B.V
• Subjects: Acyltransferase; Antigens; Bone marrow; Bone marrow transplantation; Cholesterol; Coenzyme A; Cyclosporins; Cytotoxicity; Donors; Enzymatic activity; Enzyme activity; Enzymes; Esters; Gene polymorphism; Genotypes; Graft versus host disease; Graft-versus-host reaction; Health risks; Hematology; Histocompatibility antigen HLA; In vivo methods and tests; Incidence; Leukocytes; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Methotrexate; Nucleotides; Oncology; Original Article; Polymorphism; Prophylaxis; Single-nucleotide polymorphism; Stem cell transplantation; Sterol O-acyltransferase; Transplantation; Transplants & implants; Graft-versus-host disease; Transplantation; Single nucleotide polymorphism; Donor; ACAT1
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-019-02739-2

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.