title: Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. amammen@jhmi.edu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mammen
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Diane
authors.initials: D
authors.lastname: Brisson
authors.forename: Lisa
authors.initials: L
authors.lastname: Christopher-Stine
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lloyd
authors.forename: Mary S
authors.initials: MS
authors.lastname: Leffell
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Zachary
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D001327:Autoimmune Diseases / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D059811:HLA-DRB1 Chains / Q000097:blood / Q000235:genetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000097:blood; D008137:Longitudinal Studies; D008875:Middle Aged; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D011795:Surveys and Questionnaires; D044465:White People / Q000235:genetics
chemical_list: D059811:HLA-DRB1 Chains; C509455:HLA-DRB1*11:01 antigen; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors