Apolipoprotein E Guangzhou(arginine 150 proline):一种新的脂蛋白肾病相关的基因突变

目的通过分析1个包含4个脂蛋白肾病患者的家系所有成员的载脂蛋白E (apoE)基因,寻找脂蛋白肾病相关的apoE基因突变。方法收集该家系全部成员的病史,所有成员进行尿常规、血肌酐、血脂、血清脂蛋白检查。抽提基因组DNA,PCR法扩增所有成员的apoE第4外显子。割胶纯化PCR产物后直接测序,并将纯化的PCR产物亚克隆至pMD 18-T载体,挑菌落测序。结果4例脂蛋白肾病患者和1例无症状直系亲属均携带一种新的apoE点突变的杂合子,150号密码子发生点突变:CGC→CCC(由精氨酸变成脯氨酸),伴有血浆apoE的升高。结论apoE点突变apoE Guangzhou(arginine 150 proline)可能是该家系脂蛋白肾病发病的原因。

Apolipoprotein E Guangzhou (arginine150 proline): a new variant in lipoprotein glomerulopathy

Objective To investigate the pathogenesis of lipoprotein glomerulopathy (LPG)by analyzing the apolipoprotein E(apoE)gene of members in a family ineluding four LPG patients and one asymptomatic carrier.Methods Laboratory tests for urinalysis,serum creatinine,plasma lipid and lipoprotein were performed on all the members of above family. Genomic DNA was extracted from peripheral leukocytes.The fragment of the apoE gene covering exon 4 was amplified by PCR.The gel-purified PCR products were directly sequenced and subcloned into the pMD 18-T vector.Recombinant plasmids were sequenced to investigate both alleles of patients.Results A nucleotide G to C point mutation in exon 4 of the apoE gene was confirmed in each patient and one asymptomatic member.This missense mutation encoded a new apoE variant that amino acid substitution of the proline residue for arginine residue at position 150 of apoE.Those carriers were all heterozygous of this novel point mutation apoE(arginine150 proline)with elevated plasma concentrations of apoE.Conclusions A new variant of apoE, apoE(arginine150 proline),has been identified in a family with 3 generations,including four LPG patients and one asymptomatic carrier.Study of this variant characteristics may be important for understanding the pathogenesis of LPG.