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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.