In Black participants, the Afrocentric SLCO1B1 variant c.481+1G>T was significantly associated with an increased risk of statin-induced myopathy and rhabdomyolysis (OR 3.27).
Meta-Analysis (n=6,097)
Yes
Do Afrocentric functional SLCO1B1 variants (c.481+1G>T and c.1463G>C) increase the risk of statin-induced myopathy in statin users with recent African ancestry?
Afrocentric SLCO1B1 variants (c.481+1G>T and c.1463G>C) are significantly associated with statin-induced myopathy in Black patients, highlighting the need for their inclusion in preemptive pharmacogenetic testing panels to reduce health disparities.
Effect estimate: OR 3.27 (95% CI 1.43-7.46)
p-value: p=0.005
Abstract Background Clinical pharmacogenetic implementation guidelines for statin therapy are derived from evidence of primarily Eurocentric study populations. Functional SLCO1B1 variants that are rare in these study populations have not been investigated as a determinant of statin myotoxicity and are thus missing from guideline inclusion. Objective Determine the relationship between candidate functional SLCO1B1 variants and statin-induced myopathy in people with recent genealogical ancestors from Africa. Design Population-based pharmacogenetic study using real-world evidence from electronic health record-linked biobanks Setting Various health care settings Participants Self-identified white and Black statin users with genome-wide genotyping data available. Measurements Primarily, the odds of statin-induced myopathy + rhabdomyolysis. Secondarily, total bilirubin levels. Thirdly, cell-based functional assay results. Results Meta-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 of SLCO1B1 function as well as from cell-based functional studies corroborated these findings. Limitations Data limited to severe statin myotoxicity events. Conclusion Our findings implicate Afrocentric SLCO1B1 variants 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 Source National Institutes of Health, Office of the Director - All of Us (OD-AoURP)
Yee et al. (Sun,) conducted a meta-analysis in Statin-induced myopathy and rhabdomyolysis (n=6,097). SLCO1B1 c.481+1G>T variant vs. Non-carriers was evaluated on Statin-induced myopathy + rhabdomyolysis (OR 3.27, 95% CI 1.43-7.46, p=0.005). In Black participants, the Afrocentric SLCO1B1 variant c.481+1G>T was significantly associated with an increased risk of statin-induced myopathy and rhabdomyolysis (OR 3.27).
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