Clinical immunology Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms

Abstract

In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5’ nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns.

IL-6 gene polymorphisms and sepsis in icu adult romanian patients: a prospective study

“…We first evaluated the association between variant genotype and allele of rs1800795(IL-6 -174 G/C) and sepsis risk and we could not establish any statistically significant correlation. This conclusion is different from the findings of a recent study, in which the C allele was revealed to increase pneumonia-induced sepsis risk (24), and also from the results published by many authors who studied this aspect on pediatric cohorts (12,25,26). Most of them indicated that the G allele was predictive for sepsis development: Harding et al in premature newborns, Ahrens et al in Gram-positive infections in very low birth weight (VLBW) infants, and recently, in infants with early onset sepsis (EOS) (12,25,26).…”

“…On the other hand, the major role of G allele of IL-6 -174 G/C in promoting the inflammatory response is confirmed in our study by the significant increase of IL-6 circulating levels in patients with septic shock in GG genotype but not in the other two genotypes of IL-6 -174 G/C. This finding is similar to the results of other clinical trials which demonstrate the association of GG genotype with increased circulating levels in sepsis (11,25); a single study indicates that C allele of IL-6 -174 G/C is associated with increased IL-6 levels in infants (23).…”

“…However, some reports point to the association of GG genotype with severe forms and higher mortality in systemic meningococcal infection and in certain infant populations (25,33).…”

Tumor necrosis factor-α −308G/A and −238G/A polymorphisms are associated with increased risks of sepsis: evidence from an updated meta-analysis

“…Among them, 12 studies were conducted in Asian populations , 10 in Caucasian populations , and four in mixed populations (more than two ethnic groups) . A majority of studies (80.8%) were performed in adult populations, only four studies in pediatric populations . The type of sepsis included sepsis (n = 15), severe sepsis (n = 3), septic shock (n = 2), and mixed patient groups (n = 6).…”

“…In 2010, Teuffel et al performed a systematic review and meta‐analysis and found that TNF ‐α −308G/A polymorphism was associated with sepsis but not sepsis mortality . Since 6 years have passed and more evidence has been published , it is of great value to update the results. Moreover, the study conducted by Teuffel et al only focused on TNF‐α −308G/A polymorphism .…”