Mensah Nana Yaa, Peterlongo Paolo, Steinherz Peter, Pamer Eric G, Satagopan Jaya, Papanicolaou Genovefa Anna
Department of Medicine, Service of Infectious Disease, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Biol Blood Marrow Transplant. 2009 Sep;15(9):1130-3. doi: 10.1016/j.bbmt.2009.04.012. Epub 2009 Jun 26.
The Toll-like receptor 4 (TLR4) gene is a major recognition receptor for lipopolysaccharide (LPS). In a pilot prospective study, we examined the association of 2 TLR4 polymorphisms (Asp299Gly and Thr399Ile) in the donor or the recipient with Gram-negative bloodstream infection (BSI) in 77 allogeneic hematopoietic stem cell transplant (HSCT) patients. Heterozygosity at both loci was defined as "risk genotype." The cumulative incidence of infection was estimated by treating death prior to infection as a competing risk event and compared between relevant groups using a modified chi-square test. Nine patients had the risk genotype based on donor and 5 based on recipient genotype data. Donor risk genotype showed marginal statistical significance (0.06) in univariate analysis, but not in multivariate analysis. A larger study is required to validate our findings and define genetic susceptibility to this serious infection in HSTC patients.
Toll样受体4（TLR4）基因是脂多糖（LPS）的主要识别受体。在一项前瞻性初步研究中，我们检测了77例异基因造血干细胞移植（HSCT）患者供体或受体中2种TLR4多态性（Asp299Gly和Thr399Ile）与革兰氏阴性血流感染（BSI）的相关性。两个位点的杂合性被定义为“风险基因型”。通过将感染前死亡视为竞争风险事件来估计感染的累积发生率，并使用修正的卡方检验在相关组之间进行比较。根据供体基因型数据，9例患者具有风险基因型，根据受体基因型数据，5例患者具有风险基因型。供体风险基因型在单因素分析中显示出边缘统计学意义（0.06），但在多因素分析中未显示。需要进行更大规模的研究来验证我们的发现，并确定HSCT患者对这种严重感染的遗传易感性。
