Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis

Area of Science:

• Immunogenetics
• Molecular biology
• Critical care medicine

Background:

• Sepsis, a life-threatening inflammatory response to infection, has high incidence and mortality rates.
• Interferon-gamma (IFN-γ), a key inflammatory cytokine, is implicated in the pathogenesis of sepsis.

Purpose of the Study:

• To investigate the association between functional single nucleotide polymorphisms (SNPs) in the IFN-γ gene and susceptibility to pneumonia-induced sepsis.
• To evaluate the correlation of these SNPs with sepsis severity and clinical outcomes.

Main Methods:

• Genotyping of four functional IFN-γ SNPs (-1616T/C, -764G/C, +874A/T, +3234C/T) in 196 pneumonia-induced sepsis patients and 213 healthy controls.
• Analysis of SNP distribution using chi-square or Fisher's exact tests, calculating odds ratios and confidence intervals.
• Assessment of clinical pathology, including APACHE II and SOFA scores, and discharge rates in relation to SNP genotypes and haplotypes.

Main Results:

• The -764G/C SNP showed no detectable mutations. Strong linkage disequilibrium was observed between +874A/T and +3234C/T SNPs.
• The -1616 TC+TT genotypes, +874 AT+AA genotypes, and the TAC haplotype were significantly associated with sepsis susceptibility.
• The -1616 TT genotype and +874 AA/+3234 CC genotypes demonstrated protective effects against sepsis severity, higher APACHE II/SOFA scores, and progression to severe sepsis. The CTT haplotype was associated with protection against sepsis incidence.

Conclusions:

• Functional SNPs and specific haplotypes of the IFN-γ gene are significantly associated with the susceptibility and severity of pneumonia-induced sepsis.
• These genetic variations may serve as potential biomarkers for predicting sepsis risk and progression.