Dataset Information

Association between the Lymphotoxin-? A252g Gene Polymorphism and the Risk of Sepsis and Mortality: A Meta-Analysis.

ABSTRACT: Background:The association between the lymphotoxin-? (LTA) A252G polymorphism and sepsis risk has been extensively studied, but the results have been controversial. This study is aimed at investigating the overall association between the LTA A252G polymorphism and the risk of sepsis/septic shock and sepsis-related mortality. Methods:We searched the PubMed and EMBASE databases to identify studies that investigated the association between the LTA A252G polymorphism and risks of sepsis, septic shock, and mortality. The relevant data were extracted, and statistical analyses were performed using the Revman 5.0 and STATA 12 software. Results:A total of 32 publications were included in the meta-analysis. The results demonstrated that the LTA A252G polymorphism showed no significant association with sepsis risk (GG+GA vs. AA: OR = 0.92, 95%CI = 0.79-1.07, p = 0.27) or with sepsis shock risk (GG+GA vs. AA: OR = 1.01, 95%CI = 0.84-1.22, p = 0.91). However, in the subgroup analyzed by ethnicity, the LTA A252G polymorphism significantly decreased sepsis risk in the Asian population for the recessive model [GG vs. GA+AA: OR = 0.82, 95%CI = 0.68-0.99, p = 0.04] but not in the Caucasian population. Moreover, comparisons between sepsis patients who survived and those who did not suggested that the LTA A252G polymorphism decreases the risk of mortality [GG+GA vs. AA: OR = 0.57, 95%CI = 0.41-0.80, p < 0.01]. Conclusion:Our results suggested that the A252G polymorphism in the LTA gene decreased the risk of sepsis in Asians and may reduce mortality in septic individuals.

SUBMITTER: Guo S

PROVIDER: S-EPMC7455838 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association between the Lymphotoxin-<i>α</i> A252g Gene Polymorphism and the Risk of Sepsis and Mortality: A Meta-Analysis.

Guo Shujin S Zuo Qiunan Q Li Xiaohui X He Ye Y Zhou Yutian Y

BioMed research international 20200820

<h4>Background</h4>The association between the lymphotoxin-<i>α</i> (<i>LTA</i>) A252G polymorphism and sepsis risk has been extensively studied, but the results have been controversial. This study is aimed at investigating the overall association between the <i>LTA</i> A252G polymorphism and the risk of sepsis/septic shock and sepsis-related mortality.<h4>Methods</h4>We searched the PubMed and EMBASE databases to identify studies that investigated the association between the <i>LTA</i> A252G po ...[more]

PMID: 32884945

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Project description:To investigate the significance of functional polymorphisms of inflammatory response genes by analysis of a large population of patients, both with and without severe sepsis, and representative of the diverse populations (geographic diversity, physician diversity, clinical treatment diversity) that would be encountered in critical care clinical practice.: Collaborative case-control study conducted from July 2001 to December 2005.A heterogeneous population of patients from 12 U.S. intensive care units represented by the Genetic Predisposition to Severe Sepsis archive.A total of 854 patients with severe sepsis and an equal number of mortality, age, gender, and race-matched patients also admitted to the intensive care unit without evidence of any infection (matched nonseptic controls).We developed assays for six functional single nucleotide polymorphisms present before the first codon of tumor necrosis factor at -308, IL1B at -511, IL6 at -174, IL10 at -819, and CD14 at -159, and in the first intron of LTA (also known as tumor necrosis factor-B) at +252 (LTA[+252]). The Project IMPACT critical care clinical database information management system developed by the Society of Critical Care Medicine and managed by Tri-Analytics and Cerner Corporation was utilized. Template-directed dye-terminator incorporation assay with fluorescence polarization detection was used as a high-throughput genotyping strategy. Fifty-three percent of the patients were male with 87.3% and 6.4% of Caucasian and African American racial types, respectively. Overall mortality was 35.1% in both severe sepsis and matched nonseptic control patients group. Average ages (standard deviation) of the severe sepsis and matched nonseptic control patients were 63.0 (16.05) and 65.0 (15.58) yrs old, respectively. Among the six single nucleotide polymorphisms, LTA (+252) was most overrepresented in the septic patient group (% severe sepsis; AA 45.6: AG 51.1: GG 56.7, p = .005). Furthermore, the genetic risk effect was most pronounced in males, age >60 yrs (p = .005).LTA(+252) may influence predisposition to severe sepsis, a predisposition that is modulated by gender and age. Although the genetic influences can be overwhelmed by both comorbid factors and acute illness in individual cases, population studies suggest that this is an influential biological pathway modulating risk of critical illnesses.

Dataset Information

Association between the Lymphotoxin-? A252g Gene Polymorphism and the Risk of Sepsis and Mortality: A Meta-Analysis.

Publications

Association between the Lymphotoxin-<i>α</i> A252g Gene Polymorphism and the Risk of Sepsis and Mortality: A Meta-Analysis.

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