LDLR和PCSK9基因变异与高胆固醇血症的相关研究

发布时间：2018-08-29 14:44

【摘要】：目的:本课题旨在分析高胆固醇血症患者体内血脂浓度的变化,探讨LDLR及PCSK9基因跟高胆固醇血症的相关性,为高胆固醇血症的相关防治提供实验室及遗传学依据。方法:本课题收集100例高胆固醇血症患者和50例健康体检者作为研究对象。第一部分采用全自动生化分析仪测定所有研究对象血清TC、LDL-C、Apo B100、TG、HDL-C及Lp(a)的浓度,并对检测所得结果进行统计学分析;第二部分采用PCR结合Sanger测序的方法,对所有研究对象Apo B100、LDLR与PCSK9基因进行扩增、测序,将测序结果在BLAST比对分析,观察等位基因频率并确定突变位点。结果:1.高胆固醇血症组血清TC、LDL-C、Apo B100、TG、HDL-C及Lp(a)浓度分别为7.75±1.35 mmol/L、4.70±1.83 mmol/L、1.37±0.20 g/L、1.28±0.31 mmol/L、1.35±0.39mmol/L、15.49±8.44 mg/d L;正常对照组血清TC、LDL-C、Apo B100、TG、HDL-C及Lp(a)浓度分别为3.87±0.42 mmol/L、2.65±0.28 mmol/L、0.83±0.13 g/L、1.23±0.30mmol/L、1.26±0.18 mmol/L、16.56±6.17 mg/d L。2.在高胆固醇血症患者的基因分析中,LDLR基因共检出10个突变位点,包括同义突变7个(p.C27C、p.R471R、p.P539P、p.N591N、p.V653V、p.R744R、p.S786S),错义突变2个(p.R406Q、p.D622Y),终止突变1个(p.E714X);PCSK9基因共检测出7个突变位点,包括3个同义突变(L112L、V460V、C626C),3个错义突变(p.R93C、p.V474L、p.G670E),1个框移突变(416-417ins CTG)。结论:1.高胆固醇血症组血清TC、LDL-C及Apo B100浓度高于正常对照组,且差异具有统计学意义(P0.05),可作为该病临床诊断的实验室参考指标。2.本研究正常对照组LDLR基因与PCSK9基因未发现突变位点;高胆固醇血症组检测出的LDLR基因突变位点(p.R406Q、p.D622Y、p.E714X)以及PCSK9基因突变位点(416-417ins CTG、p.R93C、p.V474L、p.G670E)可能与高胆固醇血症的发生有关。
[Abstract]:Objective: to investigate the relationship between LDLR and PCSK9 genes and hypercholesterolemia, and to provide laboratory and genetic basis for the prevention and treatment of hypercholesterolemia. Methods: 100 patients with hypercholesterolemia and 50 healthy people were studied. In the first part, the concentration of HDL-C and Lp (a) in serum of all the subjects was measured by automatic biochemical analyzer, and the results were analyzed statistically. In the second part, the method of PCR combined with Sanger sequencing was used. The Apo B100G LDLR and PCSK9 genes were amplified and sequenced. The results were compared with those of BLAST. The allele frequencies were observed and the mutation sites were determined. The result is 1: 1. 楂樿儐鍥洪唶琛，

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