载脂蛋白E基因多态性与代谢综合征的关联

Association of apolipoprotein E gene polymorphism with metabolic syndrome

目的:探讨载脂蛋白E(apolipoproteinE,ApoE)基因多态性与代谢综合征(metabolicsyndrome,MS)之间的关联。方法:将203例原发性高血压、糖尿病或原发性高血压合并糖尿病的患者分为MS组(n=96)和对照组(n=107),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)确定特定ApoE片段基因型,应用莹光标记自动测序法测定PCR产物,确认单核苷酸多态性(singlenucleotidepolymorphisms,SNPs)位点。结果:①MS组ApoEε4等位基因频率高于对照组(15.6%,8.9%,P=0.038)。②将PCR扩增产物直接测序,共检出2个SNP,均为T→C碱基转换,分别位于E4/4PCR扩增产物序列的137和210碱基处。与RFLP法检测ApoE基因型相符。③MS携带ε4的三酰甘油水平升高,高密度脂蛋白胆固醇(highdensitylipoprotien-cholesterol,HDL-C)、低密度脂蛋白胆固醇(lowdensitylipoprotien-cholesterol,LDL-C)水平均降低,其中HDL-C的ε4犤(0.97±0.20)mmol/L犦与ε3犤(1.14±0.26)mmol/L犦比较,差异有显著性意义(P=0.0009)。通过Logitic多因素回归分析发现,三酰甘油是MS独立危险因素。结论:ApoE基因的ε4等位基因是MS危险因子,ApoE可能是MS候选基因之一。

AIM:To explore the relationship between apolipoprotein E(ApoE) gene polymorphism and metabolic syndrome(MS). METHODS:Totally 203 patients with essential hypertension(EH),diabetes mellitus(DM) or EH complicated with DM were divided into two groups:MS group(n=96) and control group(n=107).ApoE genetype was determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The sequencing of the PCR product was determined with the fluorescent labeling automatic method,so as to detect single nucleotide polymorphisms(SNPs). RESULTS:①The frequency of ε4 allele was higher in the MS group than in the control group(15.6%, 8.9%, P=0.038).②Two SNPs were detected directly with sequencing of the PCR products.ApoE gene analysis showed a nucleotide substitution of T to C at the sequence of the PCR products 137 and 210 respectively in E4/4,and they were identified with the ApoE genetype determined by the RFLP method.③The triacylglycerol(TG) level was increased,the levels of high density lipoprotien-cholesterol(HDL-C) and low density lipoprotien-cholesterol(LDL-C)were reduced in the patients carrying ε4 allele in the MS group, and the HDL-C level[(0.97±0.20) mmol/L] was significantly lower than that of ε3[(1.14±0.26) mmol/L](P=0.000 9). Logistic regression analysis showed that TG was a single risk factor of MS. CONCLUSION:The ε4 allele of ApoE is the risk factor of MS,and ApoE may be one of the candidate genes of MS.