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Arthritis Care Res (Hoboken). 2012 Aug;64(8):1233-7. doi: 10.1002/acr.21671.

Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy.

Author information

1
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. amammen@jhmi.edu

Abstract

OBJECTIVE:

To investigate the association of anti-hydroxymethylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy with HLA class I and II antigens.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
22422616
PMCID:
PMC3400716
DOI:
10.1002/acr.21671
[Indexed for MEDLINE]
Free PMC Article
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