A common single nucleotide polymorphism is associated with inflammation and critical illness outcomes.
A common single nucleotide polymorphism is associated with inflammation and critical illness outcomes.
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DOI：
10.1016/j.isci.2023.108333
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发表时间：
2023-12-15
期刊：
影响因子：
5.8
通讯作者：
Vodovotz, Yoram
中科院分区：
文献类型：
--
作者：
El-Dehaibi, Fayten;Zamora, Ruben;Radder, Josiah;Yin, Jinling;Shah, Ashti M.;Namas, Rami A.;Situ, Michelle;Zhao, Yanwu;Bain, William;Morris, Alison;Mcverry, Bryan J.;Barclay, Derek A.;Billiar, Timothy R.;Zhang, Yingze;Kitsios, Georgios D.;Vodovotz, Yoram
急性炎症在危重病中是异质性的，并可预测预后。我们假设，新的，但常见的基因变异的遗传变异有助于这种异质性，并可能分层患者的结果。我们在一个推导（n = 380例钝性创伤患者）和两个验证（n = 75例创伤和n = 537例非创伤患者）队列中，通过算法搜索与551，839个SNP中任何一个相关的全身炎症介质的显著差异。该分析鉴定了LYPD 4基因中的rs 10404939。A等位基因纯合的创伤患者（rs 10404939 AA; 27%）与G等位基因纯合的患者（rs 10404939 GG; 26%）相比，全身炎症的轨迹不同，沿着多器官功能障碍（MOD）指数持续升高。创伤验证队列中rs 10404939 AA纯合子的MOD指数升高，与rs 10404939 GG纯合子相比，非创伤患者显示出更复杂的炎症网络和更差的90天生存率。因此，rs 10404939成为危重病中常见的、广泛预后的SNP。炎症失调对危重病结局有不利影响常见SNP可能与危重病中的炎症改变相关> 500，000 SNP在危重创伤和非创伤患者中进行了算法评估LYPD 4中的rs 10404939与炎症和不良结局显著相关健康科学;医学;临床遗传学
Acute inflammation is heterogeneous in critical illness and predictive of outcome. We hypothesized that genetic variability in novel, yet common, gene variants contributes to this heterogeneity and could stratify patient outcomes. We searched algorithmically for significant differences in systemic inflammatory mediators associated with any of 551,839 SNPs in one derivation (n = 380 patients with blunt trauma) and two validation (n = 75 trauma and n = 537 non-trauma patients) cohorts. This analysis identified rs10404939 in the LYPD4 gene. Trauma patients homozygous for the A allele (rs10404939AA; 27%) had different trajectories of systemic inflammation along with persistently elevated multiple organ dysfunction (MOD) indices vs. patients homozygous for the G allele (rs10404939GG; 26%). rs10404939AA homozygotes in the trauma validation cohort had elevated MOD indices, and non-trauma patients displayed more complex inflammatory networks and worse 90-day survival compared to rs10404939GG homozygotes. Thus, rs10404939 emerged as a common, broadly prognostic SNP in critical illness. Dysregulated inflammation contributes adversely to critical illness outcomes Common SNPs may associate with altered inflammation in critical illness >500,000 SNPs were assessed algorithmically in critically ill trauma and non-trauma patients rs10404939 in LYPD4 was significantly associated with inflammation and adverse outcomes Health sciences; Medicine; Clinical genetics
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影响因子：
8.8
作者：
Abboud A;Namas RA;Ramadan M;Mi Q;Almahmoud K;Abdul-Malak O;Azhar N;Zaaqoq A;Namas R;Barclay DA;Yin J;Sperry J;Peitzman A;Zamora R;Simmons RL;Billiar TR;Vodovotz Y
通讯作者：
Vodovotz Y
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
10
作者：
Zhang Y;Tedrow J;Nouraie M;Li X;Chandra D;Bon J;Kass DJ;Fuhrman CR;Leader JK;Duncan SR;Kaminski N;Sciurba FC
通讯作者：
Sciurba FC
影响因子：
17.1
作者：
Brown, David;Namas, Rami A.;Vodovotz, Yoram
通讯作者：
Vodovotz, Yoram
DOI：
10.1164/rccm.201912-2441oc
发表时间：
2020-12-15
影响因子：
24.7
作者：
Kitsios, Georgios D.;Yang, Haopu;McVerry, Bryan J.
通讯作者：
McVerry, Bryan J.