【摘要】：目的:本課題旨在分析高膽固醇血癥患者體內(nèi)血脂濃度的變化,探討LDLR及PCSK9基因跟高膽固醇血癥的相關(guān)性,為高膽固醇血癥的相關(guān)防治提供實(shí)驗(yàn)室及遺傳學(xué)依據(jù)。方法:本課題收集100例高膽固醇血癥患者和50例健康體檢者作為研究對(duì)象。第一部分采用全自動(dòng)生化分析儀測(cè)定所有研究對(duì)象血清TC、LDL-C、Apo B100、TG、HDL-C及Lp(a)的濃度,并對(duì)檢測(cè)所得結(jié)果進(jìn)行統(tǒng)計(jì)學(xué)分析;第二部分采用PCR結(jié)合Sanger測(cè)序的方法,對(duì)所有研究對(duì)象Apo B100、LDLR與PCSK9基因進(jìn)行擴(kuò)增、測(cè)序,將測(cè)序結(jié)果在BLAST比對(duì)分析,觀察等位基因頻率并確定突變位點(diǎn)。結(jié)果:1.高膽固醇血癥組血清TC、LDL-C、Apo B100、TG、HDL-C及Lp(a)濃度分別為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;正常對(duì)照組血清TC、LDL-C、Apo B100、TG、HDL-C及Lp(a)濃度分別為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.在高膽固醇血癥患者的基因分析中,LDLR基因共檢出10個(gè)突變位點(diǎn),包括同義突變7個(gè)(p.C27C、p.R471R、p.P539P、p.N591N、p.V653V、p.R744R、p.S786S),錯(cuò)義突變2個(gè)(p.R406Q、p.D622Y),終止突變1個(gè)(p.E714X);PCSK9基因共檢測(cè)出7個(gè)突變位點(diǎn),包括3個(gè)同義突變(L112L、V460V、C626C),3個(gè)錯(cuò)義突變(p.R93C、p.V474L、p.G670E),1個(gè)框移突變(416-417ins CTG)。結(jié)論:1.高膽固醇血癥組血清TC、LDL-C及Apo B100濃度高于正常對(duì)照組,且差異具有統(tǒng)計(jì)學(xué)意義(P0.05),可作為該病臨床診斷的實(shí)驗(yàn)室參考指標(biāo)。2.本研究正常對(duì)照組LDLR基因與PCSK9基因未發(fā)現(xiàn)突變位點(diǎn);高膽固醇血癥組檢測(cè)出的LDLR基因突變位點(diǎn)(p.R406Q、p.D622Y、p.E714X)以及PCSK9基因突變位點(diǎn)(416-417ins CTG、p.R93C、p.V474L、p.G670E)可能與高膽固醇血癥的發(fā)生有關(guān)。
[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，

本文編號(hào)：2211527