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Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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

Ilva Trapiņa1, / Ingrīda Rumba-Rozenfelde1 / Nikolajs Sjakste1, / Jeļizaveta Sokolovska1, , / Olga Sugoka1 / Tatjana Sjakste1

Institute of Biology, University of Latvia, Miera iela 3, Salaspils, LV-2169, LATVIA1

Faculty of Medicine, University of Latvia, Šarlotes iela 1a, Rga, LV-1001, LATVIA2

Latvian Institute of Organic Synthesis, Aizkraukles iela 21, Rga, LV-1006, LATVIA3

This content is open access.

Citation Information: Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.. Volume 63, Issue 4-5, Pages 214–221, ISSN (Print) 1407-009X, DOI: 10.2478/v10046-009-0045-2, November 2009

Publication History

Published Online:
2009-11-06

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.

Asociāciju Pētījums Starp 14Q11 - 14Q13 Proteasomu Gēnu Klastera Ģenētiskiem Variantiem Un Juvenīlo Idiopātisko Artrītu (JIA) Latvijas Populācijā

Hipotēze par iespējamo proteasomu lomu autoimūno slimību attīstībā tika izvirzīta pēc protasomālo subvienību LMP2 un LMP7 līdzdalības atklāšanas antigēnu prezentācijā. Pētījuma mērķis bija pārbaudīt iespējamo asociāciju starp proteasomālo proteīnu gēnu PSME1, PSME2 un PSMA6 alēļu variantiem un juvenīlo idiopātisko artrītu (JIA) Latvijas populācijā. Viens insercijas/delēcijas polimorfisms G-4543 CA-4544 →GA un četri viena nukleotīda polimorfismi PSMA6 gēnā un tā apkārtnē (A-2486 →G un C-1910 →T augšup no promotera, C-110 →A promoterā, un C-8 →G 5' netranslējamā apgabalā), divi cSNP PSME1 (G1457 →A: Val104, 6. ekzonā un C2536 →A: Lys244 →Thr, 11.ekzonā) un PSME2 (C1153 →G: Arg61 →Gly, 4. ekzonā un A1440 →C: His89 →Pro, 6. ekzonā) tika genotipēti, izmantojot specifisku praimeru PCR, restrikcijas vietas polimorfismu un/vai sekvencēšanu gadījumu/kontroles pētījumā 156 JIA slimniekos un 214 veselos indivīdos. Alēļu biežums un genotipu sadale bija vienādas kontroles un slimnieku grupās PSMA6 insercijas/delēcijas polimorfisma un viena nukleotīda polimorfismu: A-2486 →G, C-1910 →T un C-8 →G, gadījumos, kā arī visu pētīto PSME1 un PSME2 gēnu cSNP gadījumos. Atsevišķi analizējot atšķirības A-110 alēles un CG genotipu biežumos starp slimnieku un kontroles grupām, tās bija tuvas statistiskai ticamībai, P vērtība nedaudz pārsniedza 0.05, aditīvā modeļa izmantošana pierādīja, ka visam C-110 →G lokusam šīs atšķirības ir statistiski ticamas. Mūsu rezultāti atbalsta hipotēzi par iespējamo PSMA6 gēna alēļu asociāciju ar JIA Latvijas populācijā.

Keywords: PSMA6; chromosome 14; SNP polymorphism; juvenile idiopathic arthritis; association study

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