| Background The organic anion transporting polypeptide 1B1 (OATP1B1) is encoded by the solute carrier organic anion transporter1B1 (SLCO1B1) which is in the chromosome 12p12. The OATP1B1 transporters are presented in the basolateral membrane of hepatocytes and play a key role in the hepatic uptake of a number of endogenous and exogenous substances (including statins).Because of the SLCOIBI gene polymorphism, it will change the OATP1B1 transfer function and be an important cause of individual differences. SLCO1B1 displays a number of single nucleotide polymorphisms (SNPs). Some SNPs have been identified and some of the non-synonymous SNPs have been found to alter its transport activities. Among them, the SLCOIBI 521 T>C and 388 A>C polymorphisms were most studied. However, the findings have been controversial.Objective Previous conclusions of the association between SLCOIBI 521 T>C and 388 A>G polymorphisms and statins effectiveness have been inconsistent. We performed this meta-analysis to provide a more comprehensive estimation of this issue.Methods Electronic literatures were searched in four databases by 5 March 2014, including PubMed, Web of Science, Embase and Cochrane Library. The search was based on the following keywords:"HMG-CoA reductase inhibitor" or "statin" or "simvastatin" or "lovastatiri" or "fluvastatin" or "atorvastatini" or "pravastatin" or "rosuvastatin" or "cerivastatin" or "mevastatin", combined with "SLCO1B1". Moreover, we checked the reference lists of retrieved articles to identify more pertinent studies. Moreover, studies were considered eligible if they met all of the following criteria: ① the study explored the relationship between SLCO1B1 gene polymorphisms and the effectiveness of statins;②the SLCO1B1 521 T>C or 388 A>G polymorphism was tested in the study;③ the papers identified the sample size, distribution of alleles, genotyping assay, mean percentage change level of low-density lipoprotein cholesterol (LDL-C), total cholesterol(TC), HDL-C or triglyceride (TG);④the results were expressed as mean±standard deviation (M±SD), or other information that can help to infer the results;⑤the publication language was English. A quality assessment was performed using the Newcastle-Ottawa Scale (NOS). Meta-analysis, sub-group analysis, sensitivity analysis (RevMan 5.2) and publication bias measuring were all done (Stata 12.0).Results A total of 13 studies were included for final meta-analysis, involving 7 079 participants. Overall, there was no statistically significant association for the four genetic models of hypolipidemic effect.For the 521 T>C polymorphism, subgroup analyses suggest that significant associations were found for long-term effectiveness of lowering low-density lipoprotein cholesterol (LDL-C) in the dominant model (CC+ TC vs. TT:mean difference (MD)=1.44,95% CI:0.25-2.64,P=0.02), the recessive model (CC vs. TT+TC:MD=3.31,95% CI:0.09-6.54, P=0.04) and the homozygote comparison (CC vs. TT:MD=3.68,95% CI:0.42-6.94, P=0.03), respectively. No association found in heterozygote comparison (TC vs. TT:MD=2.00,95% CI:-9.16-13.16, P=0.73).Subgroup analyses suggest that significant associations were also found for non-Asian population of lowering LDL-C in the dominant model (CC+ TC vs. TT:MD=1.25,95% CI:0.36-2.14, P=0.006), the recessive model 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=3.33,95% CI:0.67-5.99, P=0.01), respectively. No association found in heterozygote comparison (TC vs. TT:MD=1.25,95% CI:-3.09-5.60, P=0.57).Subgroup analyses suggest that significant associations were also found for dose of statin of lowering LDL-C in the dominant model (CC+ TC vs. TT:MD=1.48,95% CI:0.27-2.69, P=0.02), the recessive model and (CC vs. TT+TC:MD= 3.76,95% CI:0.42-7.09, P=0.02) and the homozygote comparison (CC vs. TT:MD=4.13,95% CI:0.77-7.49, P=0.02), respectively. No association found in heterozygote comparison (TC vs. TT:MD=7.93,95% CI:-6.76-22.62, P=0.29).Subgroup analyses suggest that significant associations were also found for type of statin of lowering LDL-C in the dominant model (CC+ TC vs. TT:MD=1.46,95% CI:0.25-2.66, P=0.02), the recessive model and(CC vs. TT+TC:MD= 3.64,95% CI:0.50-6.78, P=0.02) and the homozygote comparison (CC vs. TT:MD=4.01,95% CI:0.75-7.26, .P=0.02), respectively. No association found in heterozygote comparison (TC vs. TT:MD=3.38,95% CI:-2.36-9.11, P=0.25).Subgroup analyses suggest that significant associations were also found for genotyping assay of lowering LDL-C in the dominant model (CC+TC vs. TT:MD=1.24,95% CI:0.20-2.29,P=0.02), the homozygote comparison (CC vs. TT:MD=2.15,95% CI:0.09-4.22, P=0.04), respectively. No association found in the recessive model (CC vs. TT+TC: MD= 1.83,95% CI:-0.16-3.82, P=0.07) and heterozygote comparison (TC vs. TT:MD=0.60,95% CI:-1.62-2.82, P=0.60), respectively.In additional, There were no significant differences for other analyses of 521 T>C or all analyses of 388 A>G.Conclusions The overall results suggest that 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 gene polymorphism has an attenuated statins effect on lowering LDL-C in non-Asain populations, the long-term effectiveness, the dose of statin, the type of statin. Moreover, the genotyping assey may impact the association between SLCOIBI 521 T>C gene polymorphism and the effectiveness of statin. |
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