Rs1982809 is a functional biomarker for the prognosis of severe post-traumatic sepsis and MODs
Rs1982809 is a functional biomarker for the prognosis of severe post-traumatic sepsis and MODs
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Rs1982809 是一种用于严重创伤后脓毒症和 MOD 预后的功能性生物标志物
DOI：
10.1177/1535370219880490
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发表时间：
2019-10-09
影响因子：
3.2
通讯作者：
Deng, Jin
中科院分区：
文献类型：
--
作者：
Gan, Lebin;Hu, Chen;Deng, Jin
BTLA是表征脓毒症患者免疫状态的有用生物标志物。我们调查了严重创伤患者BTLA基因变异与脓毒症和多器官功能障碍综合征发病率的关系。对562例严重创伤患者的BTLA基因3个Tag单核苷酸多态性进行了基因分型。为了进一步阐明其作用机制，我们测定了BTLA-3MODIFIER Letter Prime-UTR活性及其在T淋巴细胞上的表达，以进一步阐明其作用机制。只有位于BTLA的3MODIFIER字母Prime-Utr的rs1982809与脓毒症的发生率和MOD评分有显著的临床相关性。Rs1982809基因携带者的脓毒症发生率和MOD评分均高于TT基因携带者。CC型携带者外周血中BTLA+CD4+CD3+T细胞百分率明显低于CC携带者。含有C等位基因的质粒的荧光素酶活性低于T等位基因。因此，BTLA在T淋巴细胞上的差异表达可能与rs1982809 T/C诱导的3MODIFIER字母Prime-UTR活性不同有关。因此，rs1982809可作为判断脓毒症和继发性MODS预后的有用的临床生物标志物。此外，它还是一个功能性单核苷酸多态，影响BTLA 3修饰字母Prime-UTR的活性和BTLA在外周血T淋巴细胞中的表达。这项工作在严重创伤后并发症的遗传机制领域是有用的，因为它为BTLA基因多态性对脓毒症和MODS易感性的影响提供了重要的证据。这些结果是有用和重要的，因为rs1982809是一个有用的临床生物标记物，可以用来评估脓毒症和随后的MODS的预后。它也是一种功能性单核苷酸多态性，影响BTLA 3修饰字母Prime-UTR的活性和BTLA在外周血T淋巴细胞中的表达。
BTLA is a useful biomarker to characterize the immune states of sepsis patients. We investigated the association between genetic variations of BTLA and morbidity of sepsis and MODS in severe traumatic patient. Three tag single nucleotide polymorphisms of BTLA were genotyped in 562 severe trauma patients. To further elucidate the mechanism, mRNA stability, BTLA 3MODIFIER LETTER PRIME-UTR activity, and its expression on T lymphocytes were measured. Only rs1982809 which located in 3MODIFIER LETTER PRIME-UTR of BTLA showed a significant clinical relevance with the incidence rate of sepsis and MOD scores. The sepsis incidence and MOD score of rs1982809 CC genotype carriers were higher than TT carriers. The percentage of circulating BTLA + CD4 + CD3 + T lymphocytes was markedly lower in CC genotype carriers. Luciferase activity in plasmids containing C allele was lower than that of T allele. Thus, the differential expression of BTLA on T lymphocytes might be caused by the different 3MODIFIER LETTER PRIME-UTR activity induced by rs1982809 T/C. Therefore, rs1982809 is a useful clinical biomarker in the prognosis evaluating of sepsis and subsequent MODS. Moreover, it is also a functional single nucleotide polymorphism affecting the activity of BTLA 3MODIFIER LETTER PRIME-UTR and the expression of BTLA in peripheral blood T lymphocytes. Impact statement This work is useful in the field of genetic mechanism of severe post-traumatic complications, as it provides important evidence for the influence of BTLA gene polymorphism on sepsis and MODS susceptibility. The results are useful and of importance because rs1982809 is a useful clinical biomarker in the prognosis evaluating of sepsis and subsequent MODS. It is also a functional single nucleotide polymorphism affecting the activity of BTLA 3MODIFIER LETTER PRIME-UTR and the expression of BTLA in peripheral blood T lymphocytes.