The Prospective Registry of MyositIS (PROMIS): I. Next-generation sequencing identifies HLA-DQA1 as a novel genetic risk of anti-MDA5 antibody-positive dermatomyositis
Authors' conclusion
HLA-DQA1*06:01 is a new genetic and prognostic factor for anti-MDA5+ DM, potentially serving as a biomarker for early diagnosis and intervention.
Study context
- Population
- Patients with anti-MDA5+ DM, anti-MDA5⁻ DM, non-DM rheumatic disease and healthy controls (PROMIS registry)
- Participants
- 231 / 127 / 1,468 / 1,027 / 51
- Comparison
- Anti-MDA5+ DM vs anti-MDA5⁻ DM, non-DM rheumatic disease and healthy controls
- Anti-MDA5+ DMn = 231
- Anti-MDA5⁻ DMn = 127reference
- Non-DM rheumatic diseasen = 1,468reference
- Healthy controlsn = 1,027reference
- Validation anti-MDA5+ DMn = 51
- Outcome
- Genetic risk variants (human leukocyte antigen (HLA) alleles, amino acids, single nucleotide polymorphisms (SNPs)) associated with anti-MDA5+ DM
Methodological detailswhole-exome sequencing, discovery and validation cohorts
- Whole-exome sequencing
- Discovery and validation cohorts
Performance
As reported in the abstract
HLA-DQA1*06:01 prevalence
- Strongest associated amino acid HLA-DQα1:69
- P = 3.27 × 10-11
- ARHGAP22 SNP rs76208937, suggestive significance
- P = 7.99 × 10-6
Further findings
Clinical associations of HLA-DQA1*06:01 in anti-MDA5+ DM
- Acute rapidly progressive ILD
- P < 0.001
- Elevated lactate dehydrogenase
- P = 0.026
- Death
- P = 0.049
Original publication
The Prospective Registry of MyositIS (PROMIS): I. Next-generation sequencing identifies HLA-DQA1 as a novel genetic risk of anti-MDA5 antibody-positive dermatomyositis. Ann Rheum Dis. Published 17 April 2025. doi:10.
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