Methods & Results: In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy (OR1.81;95%CI:1.34, 2.45) and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36;95%CI:1.07, 1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48;95%CI:1.05,2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35,95%CI:1.10,1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34;95%CI:1.16,1.54).
Conclusion: This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins.
- Precision medicine
- Adverse Drug Reactions