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Curr Pharm Des. 2019;25(14):1663-1670. doi: 10.2174/1381612825666190705204614.

Association of SLCO1B1 and ABCB1 Genetic Variants with Atorvastatin-induced Myopathy in Patients with Acute Ischemic Stroke.

Zhang L1,2, Lv H1,2, Zhang Q3, Wang D1,2, Kang X1,2, Zhang G1,2, Li X4.

Author information

1
Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
2
Beijing Engineering Research Center of Immunological Reagents Clinical Research, Beijing 100070, China.
3
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
4
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

Abstract

BACKGROUND:

Certain patients experience muscle-related adverse effects after taking atorvastatin. Genetic factors play an important role in the occurrence of statin-induced myopathy.

AIM:

We aimed to identify genetic variants associated with statin-induced myotoxicity.

METHODS:

We prospectively enrolled 1,102 acute ischemic stroke patients who underwent atorvastatin treatment for the first time after admission. Patients were separated into case and control groups after a follow-up of 3 months. We used a biochemical definition of myopathy consisting of serum creatine kinase values more than ten times the upper limit of normal for the reference laboratory (150 U/L). Fifty single nucleotide polymorphisms (SNPs) from seven genes of ABCB1, CoQ2, HTR3B, RYR2, CYP3A5, HTR7 and SLCO1B1 were selected and genotyped. The effects of genetic polymorphisms on myopathy were observed.

RESULTS:

61 cases and 110 controls were recruited in the study. Compared with the controls, the cases had a significant higher mutant frequency of the allele A (ABCB1, rs2373588) (OR = 2.01, 95%CI = 1.10-3.67, P = 0.001) and a significant lower mutant frequency of the allele A (SLCO1B1, rs976754) (OR = 1.85, 95%CI = 1.12-3.03, P = 0.042). Genotypes or alleles of the other SNPs had no significant difference between the two groups (P > 0.05).

CONCLUSION:

Our findings reveal that SLCO1B1 and ABCB1 genetic variants are associated with statin-induced myopathy. These are valuable biomarkers for the evaluation of atorvastatin safety.

KEYWORDS:

ABCB1; SLCO1B1; acute ischemic stroke; atorvastatin; biomarkers; single nucleotide polymorphism; statin-induced myopathy.

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