Association Study of Genetic Variants in the 14q11 - 14q13 Proteasomal Genes Cluster with Juvenile Idiopathic Arthritis (JIA) in Latvian Population

Abstract

Association Study of Genetic Variants in the 14q11 - 14q13 Proteasomal Genes Cluster with Juvenile Idiopathic Arthritis (JIA) in Latvian Population The possible role of proteasomes in the development of autoimmune diseases was hypothesised after discovery of the involvement of proteasomal LMP2 and LMP7 subunits in antigene processing. The objective of this study was to determine the association between allelic variants of the genes encoding proteasomal proteins PSME1, PSME2 and PSMA6 and juvenile idiopathic arthritis (JIA) in the Latvian population. One Indel G-4543 CA-4544 →GA and four SNPs related to the PSMA6 gene (A-2486 →G and C-1910 →T, upstream promoter, C-110 →A of promoter, and C-8 →G of 5'UTR), of two cSNP in PSME1 (G1457 →A:Val104, exon 6 and C2536 →A: Lys244 →Thr, exon 11) and in PSME2 (C1153 →G:Arg61 →Gly, exon 4 and A1440 →C:His89 →Pro, exon 6) were geno-typed by means of primer-specific PCR, CAPS assay and/or sequencing in case/control study composed from the 156 JIA patients and 214 healthy individuals. Allele frequency and genotype distribution was similar in cases and controls for Indel, and SNPs A-2486 →G, C-1910 →T and C-8 →G of PSMA6, as well as for all studied cSNPs in PSME1 and PSME2 genes. Differences in A-110 allele and CG genotype frequencies were close to the statistically significant P level in JIA patients and healthy individuals, however, when an additive model was applied, the difference in the C-110 →A locus turned out to be statistically significant. The results support the hypothesis of the possible association of PSMA6 gene allelic variants with JIA in the Latvian population.