Exploring the genetic interaction between ERAP1/ERAP2 and HLA-B*52:01 in Takayasu arteritis


Casares-Marfil D., Saruhan-Direskeneli G., Grayson P. C., Tombetti E., Jiang L., Merkel P. A., ...Daha Fazla

Rheumatology, cilt.65, sa.1, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 65 Sayı: 1
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1093/rheumatology/keaf544
  • Dergi Adı: Rheumatology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, MEDLINE
  • Anahtar Kelimeler: ERAP1/ERAP2, genetics, GWAS, HLA-B*52:01, MHC-I-opathies, Takayasu arteritis
  • Marmara Üniversitesi Adresli: Evet

Özet

Objectives Takayasu arteritis is a rare vasculitis characterized by inflammation of large arteries. Given the robust genetic association with HLA-B*52:01, it was recently proposed to classify Takayasu arteritis within the spectrum of MHC-I-opathies. Although genetic associations in ERAP1 and ERAP2 have been described in several MHC-I-opathies, their role in Takayasu arteritis remains unclear. This study investigated the genetic interaction between ERAP1/ERAP2 and HLA-B*52:01 in Takayasu arteritis. Methods Using data from a large multi-ancestral GWAS, we examined the genetic association between ERAP1 and ERAP2 polymorphisms with Takayasu arteritis. Next, we conducted genetic interaction analyses between ERAP1/ERAP2 polymorphisms and HLA-B*52:01, followed by a meta-analysis across populations. In addition, we conducted a genetic association test for ERAP1/ERAP2 polymorphisms restricted to HLA-B*52:01-positive individuals. Results Our analyses suggested no significant genetic interactions between ERAP1 or ERAP2 and HLA-B*52:01 in Takayasu arteritis, which contrasts with the findings observed in other MHC-I-opathies. In addition, no significant associations between ERAP1/ERAP2 and Takayasu arteritis were detected, including analyses under dominant or recessive models, or after stratifying by HLA-B*52:01 status Conclusion These results suggest that the genetic profile of Takayasu arteritis differs from other MHC-I-opathies, supporting its classification as a distinct subtype within this group of immune-mediated diseases. These finding are hypothesis-generating, and validation in larger cohorts is warranted.