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.

中文翻译：

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ACAT1中的供体单核苷酸多态性影响骨髓移植后移植物抗宿主病的发生率

摘要

酰基辅酶A：胆固醇酰基转移酶1（ACAT1）是一种将胆固醇转换为胆固醇酯的酶。最近的一项体内研究报道，抑制ACAT1酶活性会上调T细胞的膜胆固醇水平，从而增强其细胞毒性功能。在本研究中，我们调查了是否存在ACAT1移植供体中的单核苷酸多态性rs11545566影响了116名成年患者的移植物抗宿主病（GVHD）的风险，这些患者接受了来自人类白细胞抗原相同的同胞供体的骨髓移植，并且接受了短期甲氨蝶呤和环孢素的GVHD预防。供体中AA，AG和GG基因型的频率分别为31％，45％和24％。在第100天，供者患有AA基因型与非AA基因型的患者中，II–IV级急性GVHD的累积发生率分别为6％和18％，而广泛的慢性GVHD在2年时的累积发生率分别为7％和32％，分别。多因素分析表明，供体rs11545566非AA基因型表现出II-IV级急性GVHD发生率升高的趋势（P = 0.079），并且与广泛的慢性GVHD的较高发生率显着相关（P  = 0.021）。这些结果表明供体ACAT1 rs11545566基因型可能是GVHD的预测。