Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1076910.32607/20758251-2010-2-3-72-77ArticlesСтатьиResearch ArticleAssociation of ERAP1 Allelic Variants with Risk of Ankylosing SpondylitisAssociation of ERAP1 Allelic Variants with Risk of Ankylosing SpondylitisZvyaginI Vizvyagin@gmail.comDorodnykhV YuMamedovI ZStaroverovD BBochkovaA GRebrikovD VLebedevY BShemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesInstitute of Rheumatology, Russian Academy of Medical SciencesVavilov Institute of General Genetics, Russian Academy of SciencesDNA-Technology JSCShemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences1509201023VOL 2, NO3 (2010)ТОМ 2, №3 (2010)727717012020Copyright ©; 2010, Zvyagin I.V., Dorodnykh V.Y., Mamedov I.Z., Staroverov D.B., Bochkova A.G., Rebrikov D.V., Lebedev Y.B.Copyright ©; 2010, Zvyagin I.V., Dorodnykh V.Y., Mamedov I.Z., Staroverov D.B., Bochkova A.G., Rebrikov D.V., Lebedev Y.B.2010Zvyagin I.V., Dorodnykh V.Y., Mamedov I.Z., Staroverov D.B., Bochkova A.G., Rebrikov D.V., Lebedev Y.B.Zvyagin I.V., Dorodnykh V.Y., Mamedov I.Z., Staroverov D.B., Bochkova A.G., Rebrikov D.V., Lebedev Y.B.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10769

Ankylosing spondylitis (AS) belongs to a group of autoimmune diseases affecting the axial skeleton. Beside the hla-b*27 allele, several other human genes that control the variety processes of immune homeostasis are considered to be associated with AS manifestation in different human populations. Among strong associated non-MHC genes erap 1 encoding the endoplasmic reticulum aminopeptidase 1 isoform was recently identified by single nucleotide polymorphisms (SNPs) meta analysis. In our study we inspected the genetic association of five non-synonymous coding SNPs from erapl with AS in Caucasians. We implemented the SSP-PCR system for precise genotyping of 87 hla-b*27 positive AS patients and 77 hla-b*27 healthy donors from the Russian population. Considerable differences in allele’s frequencies within patients vs control cohort were shown for 3 of 5 SNPs under investigation. Using the EM-algorhitm we reconstructed 3-marker haplotypes that distinguish with high probability two cohorts due to differences in the haplotypes frequencies. In such a way both the sensitive, CCT, haplotype and the protective, TTC, one were predicted. To verify the calculation we determined genuine frequencies of 5-marker haplotypes in AS cohort by haplotyping of individual cDNA samples using improved SSP-PCR primer set. We demonstrated that the frequencies of in silica reconstucted haplotypes and the frequencies of experimentally detected haplotypes are in a good agreement. Frequency of the risk haplotype CCT (rs17482078/10050860/2287987) detected within AS cohort reaches 88%, as well as the frequency calculated by EM-algorhitm.

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