Rheumatologic disorders

Gene Confirms Link to Ankylosing Spondylitis

HLA-B*27 positivity is related to two of the most hypomethylated loci in ankylosing spondylitis (AS), according to results of a new study presented at the 2018 ACR/ARHP Annual Meeting. 

The etiology and pathogenesis of AS are not completely understood, yet a majority of patients are believed to carry the HLA-B*27 allele. 


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For their study, the researchers performed a genome-wide DNA methylation analysis in whole blood DNA samples of 24 patients with AS, of whom 12 carried the HLA-B*27 allele and 12 did not. Patients were matched based on age, sex, and ethnicity with controls who presented with osteoarthritis.

The analysis was performed using ‘minfi’ and ‘betareg’ in R environment. Differential DNA methylation was achieved using beta regression, while adjusting for technical covariates and blood cell composition in each DNA sample.

A total of 68 differentially methylated sites were observed between patients with AS and controls. Of these, 31 were hypomethylated and 37 were hypermethylated, and represented 21 and 30 genes.

The hypomethylated genes included HCP5, POU5F1, CHD5, PON1, and RRAS2. The hypermethylated genes found included ARHGAP6, RAB11FIP3, TBC1D3H, TBC1D1, and TBCD. 

Both HCP5 and POU5F1 genes were hypomethylated in HLA-B*27-positive participants with AS, compared with HLA-B*27-negative participants with AS.

The researchers noted the importance of the hypomethylated loci in AS’s direct link to HLA-B*27 positivity.

“Our findings suggest HLA-B*27 might play a role in ankylosing spondylitis in part through ‘epigenetic linkage disequilibrium’ inducing epigenetic dysregulation,” the researchers concluded.

—Melinda Stevens

Coit P, Kaushik P, Caplan L, et al. Genome-wide DNA methylation analysis in ankylosing spondylitis. Paper presented at: 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago IL. Accessed October 26, 2018.