ApoE和SLCO1B1基因指导瑞舒伐他汀调脂的临床研究

Clinical trial of rosuvastatin in lipid regulation guided by ApoE and SLCO1B1 genes

目的为研究载脂蛋白E(ApoE)基因、溶质载体有机阴离子转运蛋白家族1B1(SLCO1B1)基因指导瑞舒伐他汀调脂的有效性及安全性。方法将血脂异常患者根据ApoE基因型分为E2组(s2/82、82/ε3)、E3组(ε3/3、82/s4)、E4组(ε3/ε4、84/ε4);根据SLCO1B1基因型分为TT组(*1a/*1a、*la/*1b、*lb/*Ib)、TC组(*la/*5、*1a/*15、*Ib/*15)、CC组(*15/*15)。所有患者均给予瑞舒伐他汀钙片,每次10mg,每晚1次,口服,持续治疗6个月。比较3组ApoE基因型患者的三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,比较3组SLCO1B1基因型患者谷丙转氨酶(GPT)、谷草转氨酶(GOT)、肌酸激酶(CK)、肌酸酐(Cr)、空腹血糖(FBG)和糖化血红蛋白(HbA1C)水平,观察研究期间患者肌痛的发生情况。结果共纳入1693例患者,其中,E2组204例、E3组1226例、E4组263例;其中,TT组1340例、TC组334例、CC组19例。经瑞舒伐他汀治疗后,E2组、E3组、E4组的TG水平分别为(1.34±1.17)、(1.20±0.43)和(1.34±0.55)mmol·L^(-1),LDL-C水平分别为(1.84±0.52)、(2.09±0.66)和(2.25±0.51)mmol·L^(-1),HDL-C水平分别为(1.20±0.26)、(1.13±0.27)和(1.01±0.21)mmol·L^(-1)。E2组的TG和LDL-C水平均较E3组和E4组显著下降,E2组和E3组的HDL-C水平均较E4组显著升高(均P<0.05)。经瑞舒伐他汀治疗后,CC组的CK水平均显著高于TT组和TC组(113us96、94U·L^(-1),均P<0.05)。TT组、TC组、CC组的肌痛发生率分别为3.13%、5.99%和10.53%,在统计学上差异均有统计学意义(均P<0.05)。结论经瑞舒伐他汀治疗后,82等位基因与E2/E3基因型能够更有效地降低血脂异常患者的TG和LDL-C水平;SLCO1B1521T>C:CC基因型患者更加容易出现肌痛现象,521T>C各基因型均未导致糖尿病出现。

Objective To study the efficacy and safety of apolipoprotein E(ApoE)gene and solute carrier organic anion transporter family 1B1(SLCO1B1)gene guided rosuvastatin in regulating lipid.Methods According to ApoE genotype,patients with dyslipidemia were divided into E2 group(ε2/2,82/ε3),E3 group(ε3/ε3,82/ε4)and E4 group(83/ε4,84/s4).According to SLCO1B1 genotype,they were divided into TT group(*la/*la,*la/*1b,*lb/*lb),TC group(*la/*5,*la/*15,*lb/*15)and CC group(*15/*15).All patients were given rosuvastatin calcium tablets 10 mg each time,once a night,orally for 6 months.The levels of triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)in three groups of ApoE genotype patients were compared.The levels of alanine aminotransferase(GPT),glutamic-oxalacetic aminotransferase(GOT),creatine kinase(CK),creatinine(Cr),fasting blood glucose(FBG)and glycated hemoglobin(HbA1C)in SLCO1B1 genotype patients in 3 groups;the occurrence of myalgia during the study period was observed.ResulstsA total of 1693 patients were included,including 204 patients in E2 group,1226 patients in E3 group and 263 patients in E4 group.Among them,there were 1340 cases in TT group,334 cases in TC group and 19 cases in CC group.After rosuvastatin treatment,the TC levels of E2,E3 and E4 groups were(1.34±1.17),(1.20±0.43)and(1.34±0.55)mmol·L^(-1);the LDL-C levels were(1.84±0.52),(2.09±0.66)and(2.25±0.51)mmol·L^(-1);the HDL-C levels were(1.20±0.26),(1.13±0.27)and(1.01±0.21)mmol.L^(-1).Compared with the E3 and E4 groups,the levels of TG and LDL-C in E2 group were significantly decreased;the HDL-C levels in E2 and E3 groups were significantly higher than that in E4 group(all P<0.05).After rosuvastatin treatment,the CK levels in CC group were significantly higher than that in TT and TC groups(113 us 96,94 U·L^(-1),all P<0.05).The incidences of myalgia in TT,TC and CC groups were 3.13%,5.99%and 10.53%(P<0.05).Conclusion After rosuvastatin treatment,82 allele and E2/E3 genotype were more effective in reducing TG and LDL-C levels in patients with dyslipidemia.SLCO1B1521T>C:CC genotype is more prone to myalgia,521T>C genotypes did not lead to diabetes.