Drs. Mammen and Christopher-Stine hold a patent for an anti-HMGCR antibody assay.
Increased frequency of DRB1*11:01 in anti–hydroxymethylglutaryl-coenzyme A reductase–associated autoimmune myopathy
Version of Record online: 27 JUL 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis Care & Research
Volume 64, Issue 8, pages 1233–1237, August 2012
How to Cite
Mammen, A. L., Gaudet, D., Brisson, D., Christopher-Stine, L., Lloyd, T. E., Leffell, M. S. and Zachary, A. A. (2012), Increased frequency of DRB1*11:01 in anti–hydroxymethylglutaryl-coenzyme A reductase–associated autoimmune myopathy. Arthritis Care Res, 64: 1233–1237. doi: 10.1002/acr.21671
- Issue online: 27 JUL 2012
- Version of Record online: 27 JUL 2012
- Accepted manuscript online: 15 MAR 2012 11:02AM EST
- Manuscript Accepted: 7 MAR 2012
- Manuscript Received: 10 JAN 2012
- Ira Fine Discovery Fund
- Dorothy and Donald Stabler Foundation
- Canadian Institutes of Health Research team in community genetics. Grant Number: CTP-82941
- Johns Hopkins University Rheumatic Diseases Research Core Center
- NIH. Grant Numbers: P30-AR-053503, K08-AR-054783
- Canada Research Chair in preventive genetics and community genomics
To investigate the association of anti–hydroxymethylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy with HLA class I and II antigens.
HLA antigens were determined in 1) 20 white and 8 African American anti-HMGCR patients, 2) 487 white and 167 African American controls, and 3) 51 white subjects with mild self-limited statin intolerance.
White anti-HMGCR patients had a higher frequency of the combination HLA–DR11, DQA5, and DQB7 than controls or statin-intolerant subjects (70% versus 17%; odds ratio [OR] 11.7 [95% confidence interval (95% CI) 4.0–35.3], P = 4.1 × 10−7 and 70% versus 21%; OR 8.3 [95% CI 2.2–33.9], P = 5.4 × 10−4, respectively). This combination was not increased in African American anti-HMGCR subjects compared to controls (13% versus 3%; OR 4.6 [95% CI 0.2–53.3], P = 0.2). However, DR11 was increased in African American anti-HMGCR patients compared to controls (88% versus 21%; OR 26.4 [95% CI 3.1–590.3], P = 0.0002). High-resolution mapping showed that 95% with DR11 had DRB1*11:01. DQA1 and DQB6 were less frequent in white anti-HMGCR–positive patients compared to controls (25% versus 65%; OR 0.2 [95% CI 0.1–0.5], P = 5.5 × 10−4 and 0% versus 45%; OR 0.0 [95% CI 0.0–0.3], P = 2.1 × 10−5, respectively). DRB11 was not associated with particular disease features.
DRB1*11:01 is associated with an increased risk of anti-HMGCR myopathy in whites and African Americans. These findings suggest a mechanistic link between statin exposure, increased HMGCR expression, and the possible presentation of HMGCR-derived peptide(s) by DRB1*11:01.