IL-6 rs1800795 polymorphism is associated with septic shock-related death in patients who underwent major surgery: a preliminary retrospective study

Abstract

BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, being the primary cause of death from infection, especially if not recognized and treated promptly. The aim of this study was to analyze whether IL-6 rs1800795 polymorphism is associated with septic shock-related death in European white patients who underwent major surgery.MethodsWe performed a retrospective study on 202 septic shock patients who underwent major cardiac or abdominal surgery. The septic shock was established according to the international septic shock definition. The primary outcome variable was the death within 90 days after diagnosis of septic shock. The IL-6 rs1800795 polymorphism was genotyped by Sequenom’s MassARRAY platform.ResultsThe median age of the patients was 73 years, 63.4% were male, and more than 40% of patients had heart disease and hypertension. Overall, the survival analysis showed that 111 (55%) patients died with a survival median of 39 days (95% CI 30.7; 47.2). The genetic analysis association with survival was performed under a recessive genetic model (CC vs. GG/CG). Patients with IL-6 rs1800795 CC genotype had higher mortality rate than the IL-6 rs1800795 GG/CG genotype at days 7 [31.6% (6/19) vs. 10.4% (19/183); log-rank test (p = 0.005)] and 28 [57.9% (11/19) vs. 33.3% (61/183); log-rank test (p = 0.009)], and 90 [68.4% (13/19) vs. 53.5% (98/183); log-rank test (p = 0.006)]. The IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death during the first 7 days [adjusted hazard ratio (aHR 4.65; p = 0.002), 28 days (aHR 2.50; p = 0.006), and 90 days (aHR 2.28; p = 0.006)] with septic shock. When patients were stratified by type of surgery, those with IL-6 rs1800795 CC genotype who underwent cardiac surgery had higher risk of death during the first 7 days (aHR 18.39; p = 0.001) and 28 days (aHR 6.1; p = 0.025) than IL-6 rs1800795 GG/GC carrier, whereas patients with IL-6 rs1800795 CC genotype who underwent abdominal surgery had higher risk of death during all follow-up (aHR 1.98; p = 0.050) than IL-6 rs1800795 GG/GC carrier.ConclusionsThe presence of IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death in patients who underwent major cardiac or abdominal surgery. These findings need robust validation in bigger independent cohorts.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0247-8) contains supplementary material, which is available to authorized users.

The association between interleukin-6 gene -174G/C single nucleotide polymorphism and sepsis: an updated meta-analysis with trial sequential analysis

“…Previous analysis also present that the frequency of IL-6 -174G/C polymorphism were rare in Asian population that resided in Korea, Japan and Shandong province and Guangxi province of China [23, 24, 46, 47]. However, two studies included in our analysis reported possible association between IL-6 -174G/C polymorphism and the risk of sepsis in the Chinese Han population in Henan province [11, 14]. This suggested that IL-6 -174G/C polymorphism was distributed in Asians that resided in certain areas and might have an influence on the pathogenesis of sepsis.…”

“…5 studies were further excluded after full-text review because of inadequate data for analysis [23–27]. Eventually, 24 studies fulfilled all criteria for inclusion, including 16 studies on the risk of sepsis, 4 studies on the mortality and 4 studies on both topics [10–14, 16–21, 28–40]. All included studies had a NOS score ≥ 6 (see Additional file 1: Table S1).…”

“…When it came to the mortality of septic patients, Lorente L et al discovered better survival of septic patients with CC genotype [13]. Jimenez-Sousa MA et al found the possible association between IL-6 -174 CC genotype and a higher septic shock-related mortality in patients who underwent major surgery [14]. These studies have controversial findings, which made us curious how they would influence the results if they were included in a new meta-analysis.…”

Gene polymorphisms and expression levels of interleukin-6 and interleukin-10 in lumbar disc disease: a meta-analysis and immunohistochemical study

“…The G to C polymorphism at position-174 of the IL-6 gene (rs1800795) causes differential activity in promoter constructs which upregulates IL-6 gene transcription [32]. The G allele of rs1800795 promotes higher circulating levels of IL-6 in patients with sepsis [33]. However, the relationship between IL-6 polymorphisms and IL-6 expression in LDD patients has not been reported.…”

Implications of IL-6 Targeting Therapy for Sepsis

“…Upon infection, IL-6 and TNFα are highly expressed by innate immune cells including macrophages and dendritic cells, whereas IFNγ is produced by IL-12−derived T helper type 1 (Th1) cells. Recently, genetic contributions of IL-6 has been also identified that single nucleotide polymorphism (SNP) at IL-6 promoter has been related to IL-6 production and associated with the risk of sepsis [6] Collectively, these findings suggests the therapeutic potential of blocking of these cytokines in development of sepsis.…”