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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-09-26

AUTHORS

Sonoko Kamoshita, Makoto Murata, Daisuke Koyama, Jakrawadee Julamanee, Shingo Okuno, Erina Takagi, Kotaro Miyao, Tatsunori Goto, Yukiyasu Ozawa, Koichi Miyamura, Seitaro Terakura, Tetsuya Nishida, Hitoshi Kiyoi

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. More... »

PAGES

112-119

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-019-02739-2

DOI

http://dx.doi.org/10.1007/s12185-019-02739-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1121304604

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/31559562


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