载脂蛋白ApoA5-1131bpT>C基因多态性与非诺贝特治疗高血脂症的相关性研究

Relationship of the polymorphism of ApoA5-1131T>C with fenofibrate treatment in hyperlipidemia efficacy response

目的研究中国高血脂人群中载脂蛋白A5(ApoA5)-1131bpT>C基因多态性与抗高血脂药物非诺贝特降脂疗效的相关性。方法本研究为前瞻性队列研究。93例初诊或停药4周以上的高血脂病人,经口给予非诺贝特200 mg.d-1(12周)。按照相关血脂变化,观察ApoA5-1131bpT>C各基因型的降血脂效果。基因型测定采用PCR-RFLP方法。研究服药前和服药后血脂的各项指标,同时检测患者各项实验室指标,χ2分析等位基因分布是否符合遗传或基因(hardy-weinberg)平衡。结果 ApoA5-1131bpT>C不同基因型携带者的TG水平有明显差异,T/C型组与C/C型组明显高于T/T型组,而以C/C型组的TG水平最高(P<0.05);经口给予非诺贝特12周后,对服药前后TG值的比较发现,T/T基因型患者下降的程度显著高于T/C组和C/C组(P<0.05),其余的血脂指标则没有此项发现。结论 ApoA5-1131bpT>C基因启动区的基因多态性与TG存在一定关联,该位点T/C转换与高血脂有关,非诺贝特的疗效按T/T组>T/C组>C/C组顺序递减。

Objective To investigate association between the polymorphism of ApoA5-1131 bpT 〉 C and anti-hyperlipidemia effect of fenofibrate in hyperlipidemia patients. Methods This was a cohort study. A total of 93 hyperlipoidemia patients were enrolled and were treated with fenofibrate for 12 weeks. The ApoA poly-morphism was identified by polymerase chain reaction-restriction fragment length polymorphism method. Lipid level of patients was measured when the study began and was over. Epidemic information and physical related data were also collected. The hardy-weinberg equilibrium for ApoA5-1131bpT 〉 C were tested using a X2 analysis. Results The level of TG is significantly different among people of various ApoA5-1131 bpT 〉 C genotypes. T/C and C/C-type group was significantly higher than the T/T-based group, and the level of TG was highest in C/C-type group （ P 〈 0.05 ）. After 12 weeks of treatment, the study found only the level of TG dropped more significantly in patients with genotype T/T than T/C group and the C/C group （P 〈 0. 05）. Other lipid indicators didn＇t have significant difference. Conclusions Plasma lipid level relate to ApoA5-1131bpT 〉 C gene polymorphism. The switch of T/C may cause high blood lipid, and atorvastatin effect descend in turn in the T/T group, T/C group and C/C group.