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SLCO1B1 A388G가 스타틴에 의한 지질감소 효과 및 근육독성 발생에 미치는 영향: 체계적 문헌고찰 및 메타분석

Effects of the SLCO1B1 A388G on Lipid-lowering Efficacy and Myotoxicity Incidence of Statins: a Systematic Review and Meta-analysis

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Objective : To investigate the effects of the SLCO1B1 A388G polymorphism on the lipid-lowering efficacy and myotoxicity incidence of statins, a systematic review and meta-analysis was conducted. Methods : The databases of PubMed, Embase, Ovid, and Cochrane Library were searched for all published studies from inception to April 2018. Using the Review Manager 5, the pooled estimates of the weighted mean difference (WMD) of the percent changes of low-density lipoprotein cholesterol (LDL-C), odds ratio (OR) and corresponding 95 % confidence intervals (CIs) were calculated. Results : A total of 12 observational studies were included in the meta-analysis of the lipid-lowering efficacy of statins. The pooled analysis showed no significant association between SLCO1B1 A388G polymorphism and LDL-C reduction (AG+GG vs AA, WMD: -0.38, 95% CI: -3.00, 2.24, p=0.77). However, in the subgroup analysis of the subjects with baseline LDL-C levels of at least 160 mg/dL, the 388G allele was significantly associated with a greater reduction in LDL-C (GG vs AA+AG, WMD: -1.78, 95% CI: - 3.12, -0.44, p=0.009; AG+GG vs AA, WMD: -2.89, 95% CI: -4.96, -0.81, p=0.006; GG vs AA, WMD: - 4.32, 95% CI: -6.93, -1.72, p=0.001). Four observational studies were eligible for meta-analysis of statin-induced myotoxicity incidence. The pooled analysis showed that SLCO1B1 A388G polymorphism was not associated with the incidence of statin-induced myotoxicity (GG vs AA, OR: 0.95, 95% CI: 0.80, 1.12, p=0.52). Conclusions : The SLCO1B1 388G allele was significantly associated with a greater reduction in LDL-C following statin therapy in the subjects with baseline LDL-C levels of at least 160 mg/dL. This result suggests that genotyping SLCO1B1 A388G polymorphism prior to statin therapy may be useful to predict an individual’s dose and potential to achieve target LDL-C levels, especially in patients with high baseline LDL-C levels.

Abstract

Objective : To investigate the effects of the SLCO1B1 A388G polymorphism on the lipid-lowering efficacy and myotoxicity incidence of statins, a systematic review and meta-analysis was conducted. Methods : The databases of PubMed, Embase, Ovid, and Cochrane Library were searched for all published studies from inception to April 2018. Using the Review Manager 5, the pooled estimates of the weighted mean difference (WMD) of the percent changes of low-density lipoprotein cholesterol (LDL-C), odds ratio (OR) and corresponding 95 % confidence intervals (CIs) were calculated. Results : A total of 12 observational studies were included in the meta-analysis of the lipid-lowering efficacy of statins. The pooled analysis showed no significant association between SLCO1B1 A388G polymorphism and LDL-C reduction (AG+GG vs AA, WMD: -0.38, 95% CI: -3.00, 2.24, p=0.77). However, in the subgroup analysis of the subjects with baseline LDL-C levels of at least 160 mg/dL, the 388G allele was significantly associated with a greater reduction in LDL-C (GG vs AA+AG, WMD: -1.78, 95% CI: - 3.12, -0.44, p=0.009; AG+GG vs AA, WMD: -2.89, 95% CI: -4.96, -0.81, p=0.006; GG vs AA, WMD: - 4.32, 95% CI: -6.93, -1.72, p=0.001). Four observational studies were eligible for meta-analysis of statin-induced myotoxicity incidence. The pooled analysis showed that SLCO1B1 A388G polymorphism was not associated with the incidence of statin-induced myotoxicity (GG vs AA, OR: 0.95, 95% CI: 0.80, 1.12, p=0.52). Conclusions : The SLCO1B1 388G allele was significantly associated with a greater reduction in LDL-C following statin therapy in the subjects with baseline LDL-C levels of at least 160 mg/dL. This result suggests that genotyping SLCO1B1 A388G polymorphism prior to statin therapy may be useful to predict an individual’s dose and potential to achieve target LDL-C levels, especially in patients with high baseline LDL-C levels.

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