Association Between the IL6 -174G/C Polymorphism and the Risk of Necrotizing Enterocolitis in Preterm Infants

¹Center for the Development of Professional Qualifications of Medical Workers, Tashkent, Uzbekistan
²Center for the Development of Professional Qualifications of Medical Workers, Tashkent, Uzbekistan

*Corresponding author: Guli Gairatovna Latipova, MD, PhD, Center for the Development of Professional Qualifications of Medical Workers, Tashkent, Uzbekistan, Phone: 9808644174, Email: [email protected], ORCID: 0009-0003-1371-3325

Received Date: August 07, 2026

Published Date: October 12, 2026

Citation: Latipova GG, Nasirova UF. (2026). Association Between the IL6 -174G/C Polymorphism and the Risk of Necrotizing Enterocolitis in Preterm Infants. Neonatal. 7(2):36.

Copyright: Latipova GG and Nasirova UF © (2026).

ABSTRACT

Background: Necrotizing enterocolitis (NEC) is one of the most serious gastrointestinal disorders affecting preterm infants and remains an important cause of neonatal morbidity and mortality. In addition to established clinical and environmental risk factors, genetic variation in inflammatory pathways may contribute to individual susceptibility to NEC. Interleukin-6 (IL-6) is a key proinflammatory cytokine involved in the regulation of inflammatory responses and has been implicated in the pathophysiology of NEC. Genetic variation in the IL6 promoter may contribute to interindividual differences in inflammatory responses.

Objective: To investigate the association between the IL6 -174G/C polymorphism (rs1800795) and the risk of necrotizing enterocolitis in preterm infants.

Methods: This comparative molecular genetic study included 157 newborns, comprising 85 preterm infants with NEC and 72 preterm infants without NEC who constituted the control group. The mean gestational age was 31.3 ± 2.0 weeks in the NEC group and 31.6 ± 1.8 weeks in the control group. The groups were comparable with respect to gestational age, birth weight, and sex distribution. The IL6 -174G/C polymorphism was analyzed using polymerase chain reaction followed by restriction fragment analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess associations between alleles and genotypes and NEC risk. Hardy-Weinberg equilibrium was assessed in the control group.

Results: The G allele was associated with higher odds of NEC compared with the C allele (OR, 2.276; 95% CI, 1.392–3.721; P < .001). The GG genotype was associated with higher odds of NEC compared with the combined CC+CG genotypes (OR, 2.381; 95% CI, 1.251–4.532; P = .008). In contrast, the CC genotype was associated with lower odds of NEC compared with the combined CG+GG genotypes (OR, 0.183; 95% CI, 0.049–0.677; P = .005). The CG genotype was not significantly associated with NEC compared with the combined CC+GG genotypes (OR, 0.714; 95% CI, 0.377–1.351; P = .299). The significant associations remained after Bonferroni correction.

In the control group (n = 72), the observed genotype distribution was CC, 12 (16.67%); CG, 33 (45.83%); and GG, 27 (37.50%). The genotype distribution did not significantly deviate from Hardy-Weinberg equilibrium (χ² = 0.125, P = .723).

Conclusions: The IL6 -174G/C polymorphism was significantly associated with NEC susceptibility in this cohort of preterm infants. The G allele and GG genotype were associated with higher odds of NEC, whereas the C allele and CC genotype were associated with lower odds. These findings suggest that IL6 -174G/C may represent a potential genetic marker for NEC risk stratification. Larger multicenter studies and functional investigations are required to validate these findings and clarify their biological significance.

Keywords: Necrotizing Enterocolitis, Interleukin-6, IL6 -174G/C, rs1800795, Genetic Polymorphism, Preterm Infants, Genetic Susceptibility