Частота встречаемости аллелей и генотипов полиморфизма гена CYP3A5 (A6986G) у детей с системной красной волчанкой

Аннотация

Ключевые слова: В статье представлены результаты анализа ассоциации системная красная полиморфизма CYP3A5 (A6986G) с развитием системной волчанка, красной волчанки (СКВ) у детей. Были обследованы дети, 45 детей с СКВ и 72 здоровых донора. Частота аллеля CYP3A5, A6986G, А составила 88,9% у пациентов против 93,75% в глюкокортикоиды, контрольной группе, различия статистически незначимы фармакогенетика, (р> 0,05). Генотип G/A был обнаружен у 54,5% пациентов и генотипирование, 47,2% здоровых людей, а G/G – у 35,6% пациентов и 45,8% иммуногенетика. в контрольной группе, без статистически значимых различий (p> 0,05). Подчеркивается потенциальная роль полиморфизма CYP3A5 как фармакогенетического маркера чувствительности к глюкокортикоидной терапии у детей с СКВ, что требует дальнейших исследований на расширенной выборке. Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by a wide range of clinical manifestations and involvement of multiple organs and systems. The features of the course of SLE in children include a more aggressive onset, high levels of immune activity, and frequent development of complications, which makes the search for prognostic markers especially important [1, 5, 11, 15]. In recent years, special attention has been paid to molecular genetic studies aimed at identifying predisposing factors for the development of SLE. Among them, 142 Жамият ва инновациялар – Общество и инновации – Society and innovations Issue – 6 № 4 (2025) / ISSN 2181-1415 polymorphisms of genes involved in xenobiotic metabolism, regulation of the immune response and apoptosis are considered as potential biomarkers of the risk and severity of the disease [2, 6, 9, 14]. The CYP3A5 gene encodes one of the key cytochromes P450 enzymes involved in the metabolism of a large number of drugs and endogenous substrates [3, 7, 10, 13]. The A6986G (rs776746) polymorphism affects the expression of the CYP3A5 enzyme, changing its activity, which may be important both in pharmacogenetics and in the pathogenesis of immune diseases, including SLE. The study of CYP3A5 (A6986G) polymorphism in children with SLE can contribute to a deeper understanding of the genetic mechanisms of predisposition to the disease and can potentially be used in predicting the course, choosing therapy and assessing the response to treatment [4, 8, 12]. Purpose of the study: to study the role of CYP3A5 gene polymorphism (A6986G) in the development of systemic lupus erythematosus in children. Materials and methods of research: We selected 45 children with SLE for molecular genetic studies. The control group consisted of 72 practically healthy individuals of Uzbek nationality (data were provided by the leading researcher of the Department of Cellular Technologies of the Institute of Immunology and Human Genomics of the Academy of Sciences of the Republic of Uzbekistan, Doctor of Medical Sciences Ruzibakieva M.R.) The material for DNA extraction was 3-5 ml of venous blood from the cubital vein (Beckton-Dickinson vacutainers were used for blood collection) with an anticoagulant/preservative of 15% tripotassium EDTA (Ethendianin-tetraacetic acid). Genotyping of polymorphic regions of immune response genes was carried out by the polymerase chain reaction (PCR) method with allele-specific primers (NPF Litekh, Moscow) and electrophoretic detection of reaction products in agarose gel. The distribution of genotypes in the studied polymorphic loci was studied using logistic regression analysis and checking for compliance with the Hardy–Weinberg equilibrium using the Fisher exact test. The correspondence of patients and control group individuals by gender and age was taken into account. Differences were considered statistically significant at p < 0.05. RESEARCH RESULTS In the first stage, we presented comparative data on the frequency of alleles A and G in patients with SLE and in the control group, and also analyzed the association with the risk of developing the disease. Table 1. Frequency of occurrence of polymorphism of gene alleles CYP3A5 (A6986G) in the general sample and in the control group in children with SLE Cases Controls OR Alleles χ2 p n = 45 n = 72 meaning. 95% CI Allele G 0.889 0.938 0.53 0.21 – 1.37 1.75 0.19 Allele A 0.111 0.063 1.88 0.73 – 4.81 143 Жамият ва инновациялар – Общество и инновации – Society and innovations Issue – 6 № 4 (2025) / ISSN 2181-1415 The results of the analysis of the frequency of alleles A and G of the CYP3A5 polymorphism (A6986G) in children with SLE compared with the control group are presented in Table 4.2. It was found that the frequency of the allele G in the group of patients was 88.9%, and in the control group – 93.8%. Despite the observed decrease in the frequency of the G allele in patients, the difference did not reach statistical significance (χ² = 1.75; p = 0.19) (Table 1). The relative risk (OR) estimate for carriage of the G allele was 0.53 (95% CI: 0.21– 1.37), indicating a possible tend