Association of IL-2 (−330 T/G) and JAK2 Val612Phe polymorphisms with the risk and severity of atopic dermatitis: a controlled, non-randomized case-control study

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease involving T-helper type 2 cells and complex immune regulation; the JAK-STAT pathway and cytokines, including interleukin-2 (IL-2), play an important role in the pathogenesis. Objective: To study the distribution of alleles and genotypes of IL-2 (-330 T/G, rs2069762) and JAK2 (Val612Phe) polymorphisms in patients with AD and evaluate their association with disease severity. Despite the established role of cytokines and the JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis, the contribution of IL-2 (-330 T/G, rs2069762) and JAK2 (Val612Phe) genetic polymorphisms to disease severity remains poorly understood, especially in certain populations. There is a lack of data on the relationship between these genetic variants and the clinical course of AD, which limits the possibilities of a personalized approach to risk assessment and disease prognosis. AIM: To study the distribution of alleles and genotypes of IL-2 (−330 T/G, rs2069762) and JAK2 (Val612Phe) polymorphisms in patients with atopic dermatitis and assess their relationship with disease severity. METHODS: The studies were conducted from February 2023 to December 2025. A total of 157 patients with AD were examined. The control group consisted of 72 conditionally healthy individuals. The study is conducted at the Tashkent State Medical University - Asmo Clinic; clinical assessment of AD severity is performed at inclusion using the standardized SCORAD scales. Genotyping of IL-2 (-330 T/G, rs2069762) and JAK2 (Val612Phe) polymorphisms is performed using the PCR-RFLP method after isolation of genomic DNA from peripheral blood. The primary endpoint is the identification of an association of these genetic polymorphisms with the presence and severity of AD; additional endpoints are the distribution of alleles and genotypes in the study groups. Statistical analysis involves comparing allele and genotype frequencies, calculating odds ratios and 95% confidence intervals, and testing the distributions for Hardy–Weinberg equilibrium; the level of statistical significance is set at p 0.05. RESULTS: JAK2 Val612Phe frequencies in the overall sample did not differ from controls (G 97%); no statistically significant associations with the risk or severity of AD were found (p 0.05). IL-2 polymorphism (−330 T/G) demonstrated an increased frequency of GG homozygotes in patients compared to controls (16.6% vs. 6.9%, respectively). Moreover, GG carriage was associated with an increased risk of AD (OR ≈ 2.6; p≈0.048). In patients with severe disease, a more pronounced association of GG and disease severity was observed (OR ≈ 4.0; p≈0.025). No study-related adverse events were recorded CONCLUSION: In the present population, the IL-2 -330 T/G polymorphism (homozygote GG) may be associated with an increased risk and severity of atopic dermatitis, while JAK2 Val612Phe does not show a significant effect. These results require confirmation in larger and more representative cohorts and, if possible, functional studies of the effect of the -330G variant on IL-2 expression. In the study sample, carriage of the GG genotype of the IL-2 polymorphism (-330 T/G) was associated with an increased risk and more severe course of atopic dermatitis, while no significant associations were found for the JAK2 Val612Phe polymorphism. These results should be interpreted taking into account the limitations of the study, including the limited sample size and the lack of a functional assessment of the effect of the -330G variant on IL-2 expression

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