HLA-B*27:04 associated with enthesitis and younger age of onset, and HLA-B allele profile in patients with ankylosing spondylitis in Thailand: A cross-sectional study

Int J Rheum Dis. 2021 Mar;24(3):411-417. doi: 10.1111/1756-185X.14055. Epub 2021 Jan 15.

Abstract

Aim: The aims of this study were to estimate human leukocyte antigen (HLA)-B allele frequency, to identify alleles associated with ankylosing spondylitis (AS), and to explore manifestations in various HLA-B*27 in Thai AS patients.

Methods: This was a cross-sectional study. Thai patients older than 18 years with diagnosed AS according to modified New York criteria who visited Siriraj Hospital (Bangkok, Thailand) were consecutively enrolled. HLA-B alleles were determined by reverse sequence-specific oligonucleotide assays, and were assigned at a 4-digit resolution. HLA-B alleles of 334 unrelated healthy Thai donors who participated in a previous phase 2b dengue vaccine clinical trial were included as controls. Odds ratio (OR) and Fisher's exact test were used to estimate association between allele and AS. The P value significance threshold was calculated according to Bonferroni.

Results: Among the 88 patients who were recruited, 34 HLA-B alleles were identified, and all patients were heterozygous. The prevalence of HLA-B*27 was 89.8%, and 4 alleles of HLA-B*27 were identified. HLA-B*27:04 (OR: 39.4, P < .0001) and HLA-B*27:05 (OR: 13.8, P = .0011) were associated with AS. In contrast, HLA-B*27:06 was not found to be associated with AS (OR: 0.4, P = .241). AS patients carrying HLA-B*27:04 were more likely to have enthesitis and younger age at onset than those carrying HLA-B*27:05.

Conclusions: HLA-B*27:04 and HLA-B*27:05 were both found to be strongly associated with Thai AS. HLA-B*27:06 showed a neutral allele for Thai AS. AS patients with HLA-B*27:04 had more enthesitis and younger age at onset than those with HLA-B*27:05.

Keywords: HLA-B*27:04; HLA-B subtype; HLA-B27; Thai; ankylosing spondylitis.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age of Onset
  • Alleles
  • Cross-Sectional Studies
  • DNA / genetics*
  • Enthesopathy / epidemiology
  • Enthesopathy / etiology*
  • Enthesopathy / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotyping Techniques
  • HLA-B27 Antigen / genetics*
  • HLA-B27 Antigen / metabolism
  • Humans
  • Incidence
  • Male
  • Polymorphism, Genetic*
  • Spondylitis, Ankylosing / complications
  • Spondylitis, Ankylosing / epidemiology
  • Spondylitis, Ankylosing / genetics*
  • Thailand / epidemiology

Substances

  • HLA-B27 Antigen
  • DNA