Polymorphisms of the Glutathione S-Transferase Genes GSTA4 and GSTP1 as Markers of Predisposition to Psoriasis and Its Clinical Features
Background: Psoriasis is a chronic immune-mediated disease of multifactorial nature with steadily increasing incidence, reaching 2-4% in the population. Despite the identification of more than 80 susceptibility loci, a significant proportion of heritable risk remains unexplained. Oxidative stress and exposure to environmental xenobiotics play a key role in the pathogenesis of psoriasis, making glutathione S-transferase enzymes, which provide detoxification and antioxidant protection, promising candidates for investigation. The aim of the study:To conduct a comprehensive analysis of the involvement of polymorphic variants of the glutathione S-transferase genes GSTA4 and GSTP1, which are highly expressed in the skin, in the molecular mechanisms of development and clinical manifestations of psoriatic disease. Materials and methods: The study included 474 patients with psoriasis and 470 healthy individuals of East Slavic origin. Genotyping of 9 single nucleotide polymorphisms of the GSTA4 and GSTP1 genes was performed using MALDI-TOF mass spectrometry. Association analysis with disease risk, clinical phenotypes (localization and pattern of lesions, psoriatic arthritis, onychodystrophy) was conducted using regression analysis and permutation testing. Functional annotation of SNPs was performed using eQTL and epigenetic databases. Results: No associations of the studied polymorphisms with overall psoriasis risk were found; however, the rs1790753 variant of GSTP1 was associated with increased disease risk in women (OR=1,31, 95%CI 1,01-1,70, Pperm=0,03). Numerous associations of GSTA4 and GSTP1 SNPs with lesions in various anatomical areas (upper and lower extremities, trunk, nails), pathomorphological changes (infiltration, Koebner phenomenon), and the development of psoriatic arthritis involving specific joint groups were identified. Functional annotation confirmed the regulatory potential of the studied variants and their tissue-specific effects on gene expression in the skin. Conclusion: The GSTA4 and GSTP1 genes do not act as factors of general predisposition to psoriasis but rather as dynamic modulators of its clinical diversity, determining lesion localization, arthritis risk, and disease course through regulation of tissue-specific gene expression. The obtained results provide a basis for developing personalized strategies for prediction, prevention, and therapy of psoriasis considering the patient's genetic profile
Saranyuk RV. Polymorphisms of the Glutathione S-Transferase Genes GSTA4 and GSTP1 as Markers of Predisposition to Psoriasis and Its Clinical Features. Research Results in Biomedicine. 2026;12(2):202-229. Russian. DOI: 10.18413/2658-6533-2026-12-2-0-3
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