Association of TNFAIP3 (rs10499194) and TNF-α (rs1800629) gene polymorphisms with susceptibility to systemic lupus erythematosus with juvenile onset and its clinical phenotypes in the Russian pediatric population

Abstract

Numerous recent studies have shown that TNFAIP3 and TNF-α gene polymorphisms are associated with susceptibility to certain autoimmune and inflammatory diseases, including systemic lupus erythematosus (SLE), systemic scleroderma, rheumatoid arthritis, psoriasis, etc. However, the results of studies on associations between these polymorphisms and the risk of developing SLE in children are ambiguous and few in number.Objective: to test the hypothesis of a possible association between the rs10499194 polymorphism of the TNFA1P3 gene and the rs1800629 polymorphism of the TNF-α gene with susceptibility to juvenile SLE (jSLE) and its clinical phenotypes in the Russian pediatric population.Material and methods. Both polymorphisms were studied by allele-specific real-time polymerase chain reaction in 63 children (15 boys and 48 girls) with a confirmed diagnosis of jSLE, whose mean age was 12.3±3.2 years (3–17 years), and the mean duration of the disease was 4.1±2.4 years. Data on the frequency of genotypes and alleles of the corresponding TNFA1P3 and TNF-α gene polymorphisms in 309 healthy unrelated blood donors over the age of 18 years (20–45 years) were used as controls.Results and discussion. The study showed that the frequency of the rs10499194T mutant allele of the TNFA1P3 gene in patients with jSLE was significantly lower compared to the control (20.6 and 30.7%; p=0.023), and its carriage slightly reduced the risk of developing SLE (odds ratio, OR 0.58; 95% confidence interval, CI 0.32–1.05, p=0.053). The frequency of the rs1800629A mutant allele of the TNF-α gene was slightly higher in jSLE compared with controls (38.1 and 26.2%, respectively; p=0.056), and its carriage slightly increased the risk of developing SLE (OR 1.73; 95% CI 0.93–3.16; p=0.056). An analysis of the frequency distribution of the rs10499194 genotypes in groups of patients with and without arthritis revealed significant differences (p=0.003). Carrying genotypes with the mutant T allele (CT+TT genotypes) in jSLE significantly reduced the risk of developing of arthritis (p=0.003). At the same time, the risk of arthritis in carriers of at least one C allele was 3.76 times higher than in carriers of the other allele (p=0.006). No relationship was found between the rs1800629 TNF-α gene polymorphism and the clinical phenotypes of jSLE.Conclusion. The rs10499194T mutant allele statistically significant reduces the risk of arthritis development as one of the clinical manifestations of jSLE, and the rs1800629A mutant allele of the TNF-α gene is associated with a tendency to increase the risk of jSLE.