Impact of SLCO1B1 (rs2306283) polymorphism on personalized atorvastatin dosing in a genetically distinct South Asian cohort

Dyslipidemia is a prevalent condition in the Pakistani population, significantly contributing to coronary heart disease (CHD). Atorvastatin, a widely used hypolipidemic drug, exhibits variable efficacy and safety influenced by genetic factors. This study aimed to assess the impact of SLCO1B1 rs2306283 (A > G) polymorphism on the efficacy and safety profile of atorvastatin in the Pakistani population. One hundred dyslipidemic patients, aged 40–75, received atorvastatin 10 mg daily for one month. Blood samples were collected on days 0 and 28 to measure lipid profiles and creatinine kinase (CK). Genotyping for rs2306283 (388 A> G) polymorphism was performed, and myopathy was evaluated using the Statin Associated Muscle Symptoms (SAMS) clinical index tool and CK levels. The minor allele frequency of rs2306283 was 12%. Only the AA (76%) and AG (24%) genotypes were observed; the GG genotype was absent. Atorvastatin significantly improved lipid parameters; however, no association was observed between rs2306283 polymorphism and lipid-lowering efficacy. A significant association was found with myopathy, with an incidence of 18.4% in patients with the AA genotype and 0% in those with the AG genotype. The G allele demonstrated a protective effect, as it was completely absent in the myopathy group. No significant elevation in CK levels was associated with myopathy. The SLCO1B1 rs2306283 polymorphism does not affect atorvastatin’s lipid-lowering efficacy; however, individuals with the AG genotype exhibit a significantly reduced risk of statin-induced myopathy in the Pakistani population. These findings support the potential role of pharmacogenetic screening in enhancing the safety of statin therapy. NCT06674044, Date: 03/09/2024.