小肠脂肪酸结合蛋白基因多态性对非诺贝特降血脂作用的影响

Effect of Polymorphism of Human Intestinal Fatty Acid Binding Protein Gene on the Therapeutic Efficacy of Fenofibrate

目的探讨小肠脂肪酸结合蛋白(IFABP)基因A54T多态性对非诺贝特降血脂作用的影响。方法选取147例原发性高脂血症患者,利用聚合酶链反应、HhaⅠ酶切、基因测序等技术检测IFABP基因型;采用生物化学方法检测服药前及服药后4周血清总胆固醇(TC)、三酯酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白AⅠ(apoAⅠ)、载脂蛋白B(apoB)等指标的变化。结果IFABP基因多态性频率分布为:A/A0·47,A/T0·37,T/T0·16;54A、54T等位基因频率分别为:0·65,0·35。服药前各组基因型携带者血脂水平差异无显著性(P>0·05)。服药4周后,A54A、A54T基因型携带者TC、TG、LDL-C、apoB水平显著下降(P<0·01),HDL-C、apoAⅠ水平显著升高(P<0·01),总有效率达97%、95%;T54T基因型携带者TG水平显著降低(P<0·05),TC、LDL-C、HDL-C、apo AⅠ、apoB水平差异无显著性(P>0·05),总有效率38%。T54T与A54A、A54T基因型相比,非诺贝特疗效差异具有显著性(P<0·01),A54A、A54T基因型间差异无显著性(P>0·05)。结论IF-ABP基因多态性与非诺贝特降血脂作用的疗效有关,纯合子T54T基因型可能对非诺贝特疗效有较强的负面影响。

Objective To explore the effect of polymorphism in codon Ala54Thr of human intestinal fatty acid-binding protein gene （IFABP） on the therapeutic efficacy of fenofibrate. Methods Totally 147 patients with hyperlipidemia [72 men mean age： （56.2 ±8.63） years; 75 women mean age： （58.4 ±9. 12） years] were enrolled. IFABP genotypes were detected by polymerase chain reaction, Hha Ⅰ digestion, and sequencing. Four weeks before and after treatment, the levels of fasting serum total cholesterol （TC） , triglyceride （TG）, high density lipoprotein-cholesterol （HDL-C）, low density lipoprotein-cholesterol （LDL-C）, apolipoprotein A Ⅰ （apoA Ⅰ ） and apolipoprotein B （apoB） were detected with biochemical techniques. Resuits The frequency of lFABP genotype was 0. 4 7 for A/ A, 0.37forA/T, and0.16forT/T, andtheallelic frequency was 0. 65 for A and 0. 35 for T. No significant differente was found in lipid levels in every genotype before treatment （P 〉 0. 05）. After 4 weeks of treatment, the levels of TC, TG, LDL-C, and apoB significantlydecreased （ P 〈 0. 01 ）, and the levels of HDH-C and apoA Ⅰ significantly increased （ P 〈 0.01 ） . The total therapeutic efficacy on A54A and A54T were 97% and 95% , respectively. In the patients with T54T genotype after treatment, no significant difference in lipids levels was found except TG （ P 〈 0. 05 ）, and the total efficacy was only 38%. The total therapeutic efficacies of fenofibrate on A54A and A54T were higher than those of T54T, and there was significant different between A54A and T54T （ P 〈 0. 01 ）. Conclusion The polymorphism of human IFABP gene in hyperlipidemia is related with the therapeutic efficacy of fenofibrate, and the T54T IFABP genotype may have strong negative effect on such efficacy.