Immunogenetic predictors of severe sepsis: role of functional polymorphisms

Thu, 28 May 2026 10:45:55 +0000

Objective.

To identify associations between functional polymorphisms in genes of the immune, endothelial, and coagulation systems and the severity and outcomes of sepsis to validate genetic risk predictors.

Materials and Methods.

This single-center prospective study included 124 patients aged of 1 month to 28 years with hematological malignancies, in whom 152 cases of sepsis were recorded. Genotyping of 20 polymorphic variants in 16 genes was performed using capillary Sanger sequencing. Statistical analysis included assessing the conformity of genotype distributions to Hardy–Weinberg equilibrium, comparing frequencies using the dominant inheritance model, and calculating odds ratio (OR), the Yates corrected χ² test, and p-value (2-tail).

Results.

The most significant predictor of an unfavorable course is the MCP1 -2518A> G polymorphism, associated with severe acute kidney injury (AKI) (OR = 3.30; p = 0.001), the need for renal replacement therapy (OR = 5.4; p<0.0001), mechanical ventilation (p = 0.019) and mortality (OR = 2.4; p = 0.02). MTHFR c.665C > T is associated with sepsis-induced coagulopathy (OR = 2.0; p = 0.049), DIC (OR = 2.9; p = 0.003) and proinflammatory phenotype SIRS (OR = 2.17; p = 0.04). A dual role was determined for HAVCR1: c.619A> G is protective against septic shock (OR = 0.42; p = 0.02) and AKI (OR = 0.34; p = 0.007); c.536T > C is associated with mortality (OR = 3.7; p = 0.02). Opposite effects of IL18: -607C >A – risk of renal replacement therapy (OR = 3.3; p = 0.008) and mechanical ventilation (OR = 2.4; p = 0.009); -137G > C – protection against these complications (OR = 0.46 and 0.32, respectively). The context dependence of TNFα -308G >A was established: it was associated with coagulopathy (OR = 4.10; p = 0.02) and protective for chronic critical illness (OR = 0.18; p = 0.001). Polymorphisms of TLR4 (c.296A> G, c.596C > T) and IL18 (-137G > C) were associated with the risk of sepsis recurrence (OR = 4.0; p = 0.03). The TLR4 variant c.*1205G >A was associated with septic shock (OR = 2.2; p = 0.04). PAI-1 4G/5G was associated with severity of AKI (OR = 2.62; p = 0.009), and the protective allelic variant CD14 c.-159C > T was associated with reduced risk of chronic critical illness (OR = 0.36; p = 0.0054).

Conclusions.

Genetic markers associated with the development of key sepsis complications were identified. The obtained results substantiate the usefulness of genetic testing for risk stratification and personalized intensive care in patients with sepsis.

Gorbich O.A. on КМАХ

Immunogenetic predictors of severe sepsis: role of functional polymorphisms

Objective.

Materials and Methods.

Results.

Conclusions.