Study of the role of tumor necrosis factor-α (–308 G/A) and interleukin-10 (–1082 G/A) polymorphisms as potential risk factors to acute kidney injury in patients with severe sepsis using high-resolution melting curve analysis

Abstract

Rational: Septic acute kidney injury (AKI) is a prevalent complication in intensive care units with an increased incidence of complications.Objective: The aim of the present study was to assess the use of high-resolution melting curve (HRM) analysis in investigating whether the genetic polymorphisms; –308 G/A of tumor necrosis factor-α (TNF-α), and –1082 G /A of Interleukin-10 (IL-10) genes may predispose patients diagnosed with severe sepsis to the development of AKI.Methods: One hundred and fifty patients with severe sepsis participated in the present study; only sixty-six developed AKI. Both polymorphisms were studied using HRM analysis.Main findings: The low producer genotype of both studied polymorphism of TNF-α and IL-10 genes was associated with AKI. Using logistic regression analysis, the low producer genotypes remained an independent risk factor for AKI. A statistically significant difference was detected between both studied groups as regards the low producer genotype in both TNF-α (–308 G/A) and interleukin-10 (IL-10) (–1082 G/A) polymorphisms being prevalent in patients developing AKI.Principle conclusions: The low producer genotypes of both TNF-α (–308 G/A) and IL-10 (–1082 G/A) polymorphisms could be considered a risk factor for the development of AKI in critically ill patients with severe sepsis, thus management technique implemented for this category should be modulated rescuing this sector of patients from the grave deterioration to acute kidney injury. Using HRM for genotyping proved to be a highly efficient, simple, cost-effective genotyping technique that is most appropriate for the routine study of large-scale samples.

Association between inflammatory-response gene polymorphisms and risk of acute kidney injury in children

“…Our results were similar to several other previous works, which found no association between the rs1800629 polymorphism and AKI susceptibility [32–34]. However, there were also some previous works which demonstrated an association between the polymorphism and AKI risk (or severity), although conflicting results have been reported [35–37]. These findings demonstrate the complexity of the association, and further studies will be needed for comprehensive elucidation of the role of the polymorphisms in influencing AKI risk.…”

“…In this work, we also failed to find an association of the interleukin gene polymorphisms ( IL6 rs1800795, IL6 rs1800796, IL6 rs1800797, IL10 rs1800896, IL10 rs3021097, IL18 rs1946518 and IL18 rs187238) with AKI risk. Among these polymorphisms, IL6 rs1800795 and IL10 rs1800896 have been previously investigated with regard to their association with AKI risk [35,36]. Our finding on IL6 rs1800795 polymorphism agreed to the only previous report on this aspect [36].…”

“…Our finding on IL6 rs1800795 polymorphism agreed to the only previous report on this aspect [36]. However, both previous studies on IL10 rs1800896 polymorphism showed that the polymorphisms could be associated with AKI risk, which was in contrast with our work [35,36]. The difference between findings in our work and those in previous work could be justified by four explanations.…”

Kidney Injury and Repair Biomarkers in Marathon Runners

“…32,33 Lastly, TNF-α, which is mainly produced by macrophages, has also been associated with AKI in patients with severe sepsis. 34 …”

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

“…Variations in or nearby genes related to inflammation, circulation, and cell survival have been suggested in candidate polymorphism studies regarding AKI [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. Additionally, the first hypothesis-free studies in AKI genetic predisposition have been published [28,29,30], with some replicated associations [31].…”