Lipopolysaccharide binding protein promoter variants influence the risk for Gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation
Lipopolysaccharide binding protein promoter variants influence the risk for Gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation
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DOI：
10.1182/blood-2007-09-101709
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发表时间：
2008-02-15
期刊：
影响因子：
20.3
通讯作者：
Clark, Joan G.
中科院分区：
文献类型：
--
作者：
Chien, Jason W.;Boeckh, Michael J.;Clark, Joan G.
脂多糖结合蛋白（LBP）的功能取决于循环LBP水平。LBP转录调控的紊乱可能影响临床事件的风险。在一项巢式病例对照研究中，使用单核苷酸多态性单倍型标记（tagSNP）方法，我们评估了LBP基因的遗传变异是否会影响异基因造血细胞移植（HCT）后革兰氏阴性（GN）菌血症的风险，然后通过将遗传变异与基础血清LBP水平和死亡率相关来验证前瞻性队列中的相关性。患者中tagSNP 6878 C等位基因的存在与GN菌血症的2倍高风险相关（比值比= 2.15; 95%置信区间[Cl]，1.31-3.52，P = .002）。TagSNP 6878与LBP启动子中的3个SNPs存在强连锁不平衡，其中一个SNP 1683（r（2）= 0.8）位于调节LBP启动子效率的CAAT盒中。SNP 1683与较高的中位基础血清LBP水平（TT 8.07 μ g/mL; TC 10.40 μ g/mL; CC 17.39 μ g/mL; P = .002）以及HCT后GN菌血症相关死亡率增加5倍相关（风险比= 4.83; 95%CI，1.38-16.75，P = .013）。这些数据表明，LBP基因的转录调控有助于发展GN菌血症和HCT后死亡的风险。
Lipopolysaccharide binding protein (LBP) function is dependent on circulating LBP levels. Disturbance of LBP transcription regulation may influence the risk for clinical events. In a nested case-control study using a single nucleotide polymorphism haplotype tagging (tagSNP) approach, we assessed whether genetic variation in the LBP gene influences the risk for Gram-negative (GN) bacteremia after allogeneic hematopoietic cell transplantation (HCT), then validated the association in a prospective cohort by correlating genetic variation with basal serum LBP levels and mortality. Presence of the tagSNP 6878 C allele among patients was associated with a 2-fold higher risk for GN bacteremia (odds ratio = 2.15; 95% confidence interval [Cl], 1.31-3.52, P = .002). TagSNP 6878 was in strong linkage disequilibrium with 3 SNPs in the LBP promoter, one of which was SNP 1683 (r(2) = 0.8), located in a CAAT box that regulates LBP promoter efficiency. SNP 1683 was associated with higher median basal serum LBP levels (TT 8.07 mu g/mL; TC 10.40 mu g/mL; CC 17.39 mu g/mL; P = .002), and a 5-fold increase in GN bacteremia related mortality after HCT (hazard ratio = 4.83; 95% Cl, 1.38-16.75, P = .013). These data suggest that transcriptional regulation of the LBP gene contributes to the risk for developing GN bacteremia and death after HCT.