Association of
IFN
‐γ +874 T/A Polymorphism With
COVID
‐19 Susceptibility, Severity, and Inflammatory Response: A Case–Control Study From Southern I
Nasir Arefinia, Bahman Aghcheli, Seyed Mohammad Ali Hashemi, Zohreh‐al‐sadat Ghoreshi, Emad Behboudi ABSTRACT
Background
Significant interpatient variability in Coronavirus Disease 2019 (COVID‐19) manifestations highlights the influence of host genetic factors on disease outcomes. This study examines its association with COVID‐19 susceptibility, severity, and inflammatory markers in an Iranian population.
Methods
A retrospective case–control analysis was performed on 210 COVID‐19 patients and 210 age‐ and sex‐matched control subjects to evaluate whether the Interferon‐gamma (IFN‐γ) gene polymorphism (+874 T/A) is associated with disease severity.
Results
Patients had more comorbidities (e.g., diabetes 26.2% vs. 14.3%; hypertension 29.5% vs. 16.7%) and pronounced paraclinical abnormalities, including elevated Neutrophil‐to‐Lymphocyte Ratio (NLR) (8.1 vs. 1.9), C‐reactive protein (CRP) (45.5 vs. 3.2 mg/L), and lymphopenia (1.1 vs. 2.1 × 10 3 /μL; all p < 0.001). The TA genotype and A allele increased disease susceptibility (Odds Ratio (OR) =2.05 (95% CI: 1.32–3.19), p = 0.002; OR = 1.58 (95% CI: 1.11–2.25), p = 0.01, respectively). The TA genotype independently predicted severe disease (aOR = 2.85, p = 0.001), and both the TA and AA genotypes were linked to higher IL‐6 levels ( p < 0.001). TT carriers had shorter hospitalizations ( p < 0.01). Combining TA/AA with NLR improved severity prediction (AUC = 0.82 (95% CI: 0.76–0.88)).
Conclusion
The IFN‐γ +874 TA genotype was independently associated with severe COVID‐19. The TA genotype appears to confer increased risk of severe disease, whereas the AA genotype may be linked to a milder clinical presentation despite elevated inflammatory markers. Integration of genetic and hematological parameters may enhance risk stratification; however, further validation in larger and diverse populations is warranted.