Functional Polymorphisms of Interferon-gamma Affect Pneumonia-Induced Sepsis

Abstract

ObjectiveSepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ) plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs) that may be associated with sepsis.MethodsA total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate. Four functional SNPs, −1616T/C (rs2069705), −764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson’s chi-square test or Fisher’s exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated.ResultsNo mutations in the IFN-γ −764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD) (r2 = 0.894). The −1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of −1616 TT wasn’t only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either.ConclusionOur results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium

“…Likewise, we hypothesized that IL8 rs2227307 and IL12B rs3212227 intronic polymorphisms affect alternative splicing of IL8 and IL12B mRNA and even alter mRNA expression, thereby dysregulating IL8-and IL12-mediated Th1 immune responses against fungal pathogens. In line with these arguments, a number of previous studies have reported associations of these polymorphisms with immune-related diseases (55,56) and infections (57)(58)(59)(60), including IA (45). In particular, we confirmed an association previously reported by Mezger (45).…”

IFN‐γ +874T/A polymorphism increases susceptibility to post‐traumatic osteomyelitis

“…Previous studies reported that IFN‐γ +874T/A polymorphism might be associated with the risk of developing several kinds of inflammatory disease, such as SARS (Chong et al, ), tuberculosis (Mabunda et al, ) and pneumonia‐induced sepsis (Wang et al, ). The underlying mechanism for the significant association between IFN‐γ gene polymorphism and the risk of post‐traumatic osteomyelitis may be linked to peripheral levels of IFN‐γ, which are regulated by IFN‐γ gene polymorphism.…”

Cytokines of the Immune System

“…8 IFN-γ gene polymorphisms (SNP: rs1861493, and microsatellite CA together with others unrelated to IFNG) showed significant allelic associations with the idiopathic inflammatory myopathies in a UK Caucasian population. 9 In atopic asthma the association of the IFNG-gene +2109 A>G (rs1861494) SNP polymorphism (A/G) was observed in a case-control cohort study, which was replicated in a family study.…”