SLCO1B1functional variants and statin-induced myopathy in people with recent genealogical ancestors from Africa: a population-based real-world study

Abstract

AbstractBackgroundClinical pharmacogenetic implementation guidelines for statin therapy are derived from evidence of primarily Eurocentric study populations. FunctionalSLCO1B1variants that are rare in these study populations have not been investigated as a determinant of statin myotoxicity and are thus missing from guideline inclusion.ObjectiveDetermine the relationship between candidate functionalSLCO1B1variants and statin-induced myopathy in people with recent genealogical ancestors from Africa.DesignPopulation-based pharmacogenetic study using real-world evidence from electronic health record-linked biobanksSettingVarious health care settingsParticipantsSelf-identified white and Black statin users with genome-wide genotyping data available.MeasurementsPrimarily, the odds of statin-induced myopathy + rhabdomyolysis. Secondarily, total bilirubin levels. Thirdly, cell-based functional assay results.ResultsMeta-analyses results demonstrated an increased risk of statin-induced myopathy + rhabdomyolysis with c.481+1G>T (odds ratio [OR] = 3.27, 95% confidence interval [CI] 1.43-7.46,P=.005) and c.1463G>C (OR = 2.45, 95% CI 1.04-5.78,P=.04) for Black participants. For White participants, c.521T>C was also significantly associated with increased risk of statin-induced myopathy + rhabdomyolysis (OR = 1.41, 95% CI 1.20-1.67,P=5.4x10−5). This effect size for c.521T>C was similar in the Black participants, but did not meet the level of statistical significance (OR = 1.47, 95% CI 0.58-3.73,P=0.41). Supporting evidence using total bilirubin as an endogenous biomarker ofSLCO1B1function as well as from cell-based functional studies corroborated these findings.LimitationsData limited to severe statin myotoxicity events.ConclusionOur findings implicate AfrocentricSLCO1B1variants on preemptive pharmacogenetic testing panels, which could have an instant impact on reducing the risk of statin-associated myotoxicity in historically excluded groups.Primary Funding SourceNational Institutes of Health, Office of the Director - All of Us (OD-AoURP)