Endoplasmic reticulum aminopeptidase-1 polymorphism increases the risk of rheumatoid arthritis


Akbulut E., YILDIRIM T., ÖZTÜRK O.

TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI, cilt.47, sa.4, ss.465-473, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 47 Sayı: 4
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1515/tjb-2022-0007
  • Dergi Adı: TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.465-473
  • Anahtar Kelimeler: autoimmunity, ERAP1, genetic predisposition, peptide presentation, rheumatoid arthritis, CRYSTAL-STRUCTURE, ERAP1, POPULATION, ER, ASSOCIATION
  • İnönü Üniversitesi Adresli: Evet

Özet

Objectives Endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphic changes cause autoimmunity. To understand the contribution of ERAP1 to the occurrence of rheumatoid arthritis (RA) disease, we investigated the relationship between ERAP1 and RA. Methods This study was conducted with 201 patients and 171 healthy controls. The rs26653, rs27044, rs27582, rs28096, and rs30187 polymorphic regions of ERAP1 were investigated. The comparison was done with Arlequin software and logistic regression. Haplotypes were analyzed with Phylogenetic Network software. ERAP1 was modeled using Promod3. Topological changes in ERAP1 were analyzed with TM-Score. Results The results showed that rs26653G>C (p=0.002, OR=2.001, 95%CI=1.276-3.137), rs27044C>G (p=0.037, OR=1.583, 95%CI=1.028-2.440), rs27582G>A (p<0.05, OR=0.348, 95%CI=0.194-0.622) and rs30187C>T (p=0.006, OR=1.849, 95%CI=1.191-2.870) polymorphisms are associated with RA disease risk. The relationship between rs28096 polymorphism and RA disease risk could not be determined (p=0.509). The risk haplotype for rheumatoid arthritis was determined as [CGAAT]. It was determined that polymorphisms of ERAP1 cause changes in the entry pocket of substrate and ligand. Conclusions We report a haplotype [CGAAT] that is associated with RA risk from Turkey that has not been described before. These data will make important contributions to elucidating the molecular mechanism of RA.