Association between SLCO1B1 521 T>C and 388 A>G Polymorphisms and Statins Effectiveness: A Meta-Analysis

J Atheroscler Thromb. 2015 Aug 26;22(8):796-815. doi: 10.5551/jat.26856. Epub 2015 Apr 1.

Abstract

Aim: Previous studies on the association between the SLCO1B1 521 T>C and 388 A>G polymorphisms and statin effectiveness have been inconsistent. We performed this meta-analysis to provide a more comprehensive estimation of this issue.

Methods: Multiple electronic literatues databases were searched on March 5th 2014. A quality assessment was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. A meta-analysis, sub-group analysis, sensitivity analysis (RevMan 5.2), publication bias measuring and meta-regression analysis were conducted utilizing the Stata software program (version 12.0).

Results: A total of 13 studies were included in the final meta-analysis, which included 7,079 participants. Overall, there was no statistically significant association in the four genetic models of hypolipidemic effect. For the 521 T>C polymorphism, significant associations were found for the long-term effectiveness of lowering the low-density lipoprotein cholesterol (LDL-C) and in non-Asian populations in the dominant model [(CC+TC vs. TT: mean difference (MD)=1.44, 95% CI: 0.25-2.64,p=0.02) and (CC+TC vs. TT: MD=1.38, 95% CI: 0.28-2.49, p=0.01)], the recessive model [(CC vs. TT+TC: MD=3.31, 95% CI: 0.09-6.54, p=0.04) and (CC vs. TT+TC: MD=2.83, 95% CI: 0.26-5.41, p=0.03)], and the homozygote comparison [(CC vs. TT: MD=3.68, 95% CI: 0.42-6.94,p=0.03) and (CC vs. TT: MD=3.33, 95% CI: 0.67-5.99, p=0.01)], respectively. There were no significant differences for the other analyses of the 521 T>C polymorphism or all the analyses of the 388 A>G polymorphism.

Conclusions: The overall results suggest that the SLCO1B1 521 T>C and 388 A>G polymorphisms do not affect the lipid-lowering effectiveness of statins. However, allele C of the SLCO1B1 521 T>C polymorphism leads to an attenuated effect on lowering the LDL-C in non-Asian populations and the long-term effectiveness of statin treatment.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / genetics*
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters / genetics*
  • Polymorphism, Genetic*
  • Treatment Outcome

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human