Polymorphism of the SLC7A11-PCDH18 locus may be a novel genetic risk factor for juvenile idiopathic arthritis

The rs13128867 (T>C) polymorphism located between SLC7A11 and PCDH18 genes was originally described as a new susceptibility locus for Kawasaki disease (KD) in the Chinese population. Focusing on the identification of risk alleles for juvenile-onset autoimmune rheumatic diseases, the presented paper aims to demonstrate the results of the study undertaken to investigate an association between the rs13128867 polymorphism and KD, juvenile idiopathic arthritis (JIA), and juvenile systemic lupus erythematosus (JSLE) in Caucasians living in Belarus. In total, 675 children and adolescents under 17 at the onset of the disease were included in the study performed, and 386 out of them were without any autoimmune, inflammatory, or joint disorders and served as the clinical control. Genomic DNA samples were genotyped using the real-time PCR technique. Case-control comparison was adjusted for sex with a view of reducing uneven gender distribution between the groups, and p-values were adjusted with the Benjamini-Hochberg procedure. The rs13128867 minor C allele frequency in the control group was found to be 17.6% that is close to other European populations. At the same time, an associative analysis of the rs13128867 polymorphism with KD did not replicate the data known for the Chinese population. Further analysis revealed an association between the rs13128867 minor allele with JIA (OR = 1.50, 95% CI 1.11-2.03, padj = 0.027) and oligoarthritis - the most common JIA subtype (OR = 1.67, 95% CI 1.17-2.39, padj = 0.016). A tendency to association of the rs13128867 minor allele and JSLE was also observed. Thus, the study results demonstrated for the first time that the SLC7A11-PCHD18 rs13128867 polymorphism may be a novel genetic risk factor for JIA in Caucasian patients. However, a further investigation into the rs13128867 polymorphism is strongly required.

SLC7A11, PCDH18, rs13128867, genetic risk factor, Kawasaki disease, juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, autoimmune diseases

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