Association Study Between SNPs Of SLCO1B1?ABCB1 With Statin's Effection

Cardiovascular disease is the leading cause of disability and death,and the elevated blood lipids level is one of the major risk factors for cardiovascular disease.Therefore,antilipemic agent is an important measured for the prevention and treatment of atherosclerosis and cardiovascular disease.Statins is the one of the most widely used antilipemic agent in the world,however,the metabolism suppression of statins will affect the its drug efficacy,even have some side effects and cause disease such as adenomyosis.SLCO1B1,CYP3A4?CYP3A5 and ABCB1 gene encoding protein that is responsible for the protein which in the transportation and metabolic pathways of statins.Moreover,the gene polymorphism influent the function of these proteins,thus affecting the curative effect.Therefore,our research mainly focus on the influence of 12 SNPs of SLCO1B1,CYP3A4?CYP3A5,ABCB1 on the curative effect of stains.The objects of our study are patients with coronary heart disease in cardiovascular department of St.John's hospital in Kunming,in the period from December 2014 to December 2016.The total cases numbers of patients are 1100,and 287 of them with complete follow-up information.According to the principle of informed consent,we collected peripheral blood samples of these patients and extracts leucocyte DNA from these blood samples.The SNaPshot method was applied for genotyping on 12 gene polymorphism loci in SLCO1B1,CYP3A4?CYP3A5 and ABCB1 gene of the 287 patients,respectively.STATA12.0 were used to statistically analysis the relevance between gene polymorphism and the antilipemic efficacy of statins.Results:We found 4 loci(rs2291075 rs11045820,rs11045818,rs1045642)genetic polymorphism in these 287 samples.Logistic regression analysis results for these 4 sites are as follow:(1)In the dominant model of rs2291075 site in SLCO1B1 gene,C/C and C/T genotype significantly enhanced the curative effect of statins to reduce LDL-C level(OR = 1.05,95%Cl:1.00 1.10,p=0.03).In implicit model,no genotype significantly changed the lipid-lowering efficacy of stains;however,in additive model,the C allele tend to improving statin's lipid-lowering efficacy even the differency is not significant.(2)In the dominant model of rs11045820 site in SLCOIBI gene,T/T genotype have shown that the curative effect of statins that increase HDL-C(OR = 0.97,95%CI:0.92 1.01,p = 0.022).and reduce TG significantly(OR = 0.98,95%CI:0.93 1.03.p ?0.023).In implicit model,C/C genotype can significantly increase the curative effect of statins to reduce LDL-C level(OR = 1.12,95%CI:1.01 1.24,p = 0.028).In additive model.C allele can weaken the effect of statins to increase the HDL-C(OR = 0.67,95%CI:0.45 1.00,p = 0.048)and reduce the TC significantly(OR = 1.57,95%CI:1.03 2.41,p = 0.036).(3)In the dominant model of rs11045818 site in SLCO1B1 gene,C/C and C/T genotype significantly enhanced the curative effect of statins to reduce the TG level(OR = 0.96,95%CI:0.90 1.02,p = 0.031).In implicit model,there is no genotype that can significantly change the lipid-lowering efficacy of statins;however,In additive model,the C allele tend to improving statin's lipid-lowering efficacy even the differency is not significant.(4)In the dominant model of rs1045642 site in ABCB1 gene,T/T genotype significantly enhanced the curative effect of statins to reduce the LDL-C level(OR = 0.95,95%Cl:0.90 1.00,p = 0.041).In implicit model,C/C genotype significantly enhanced the effectiveness of stains to reduce TG level(OR = 0.93,95%Cl:0.880.98,p = 0.006).In additive model,the allele C tend to improving statin's lipid-lowering efficacy even the differency is not significant.Then,we applied meta-analysis to find the correlation between SLCOIBI c.521 T>C polymorphism and the efficacy of statins,the results showed that T/T genotype have stronger lipid-lowering efficacy when treated by stains[LDL-C:WMD:2.81(0.14,0.14),P = 0.039;TC:WMD:1.57(0.18,0.18),P = 0.027],ABCB1 gene c.3435 c>T polymorphism loci T/T genotype showed significantly lipid-lowering efficacy of statins[LDL-C:WMD:2.57(5.05,0.10),P = 0.042;TC:WMD:2.12(4.09,0.14),P = 0.036].To sum up,among the population of Yunnan province in China,rs2291075 site in SLCOIBI genes has significant correlation with the curative effect of statins to reduce LDL-C level.Rs11045820 in SLCOIBI gene has significant correlation with the curative effect of statins to reduce LDL-C,TC,and TG level,and to increase HDL-C level significantly.rs11045818 site in SLCOIBI gene was significantly associated with the curative effect of statins to decrease TG level.Rs1045642 site in ABCB1 gene shows significant relevance to the efficacy of statins to reduce LDL-C and TG level.