综述

中国人群家族性高胆固醇血症LDLR基因突变研究进展

展开
  • 首都医科大学附属北京安贞医院, 北京市心肺血管疾病研究所, 北京 100029

收稿日期: 2010-08-03

  修回日期: 2010-10-14

  网络出版日期: 2011-01-20

基金资助

国家自然科学基金项目(编号: 30771986, 30772356)和北京市自然科学基金项目(编号: 7062010, 7092016)资助

Research progression of LDLR mutations in Chinese Familial hyper- cholesterolemia

Expand
  • Beijing Institute of Heart Lung and Blood Vessel Diseases-Beijing Anzhen Hospital, Affiliated of Capital Medical University, Beijing 100029, China

Received date: 2010-08-03

  Revised date: 2010-10-14

  Online published: 2011-01-20

摘要

家族性高胆固醇血症(Familial hypercholesterolemia, FH)主要是由于低密度脂蛋白受体(Low-density lipoprotein receptor, LDLR)基因突变导致的单基因显性遗传性疾病。FH患者LDLR基因突变导致细胞膜表面LDLR减少或缺如, 机体代谢胆固醇能力降低, 血浆胆固醇增高并沉积在不同的组织和器官, 常伴有全身黄色瘤和早发冠心病, 因此FH也是最常见的严重代谢性疾病。世界范围内对LDLR基因突变的报道总共有1 741种, 经整理我国目前报道的140例FH指示病例, 包括108种LDLR基因突变类型。文章对已报道的中国FH患者LDLR基因突变特点进行系统分析和综述, 旨在为FH诊断治疗提供参考依据。

本文引用格式

代艳芳,孙立元,张新波,王绿娅 . 中国人群家族性高胆固醇血症LDLR基因突变研究进展[J]. 遗传, 2011 , 33(1) : 1 -8 . DOI: 10.3724/SP.J.1005.2011.00001

Abstract

Familial hypercholesterolemia (FH), one monogenic autosomal dominant disease, mainly results from genetic defects in the low-density lipoprotein receptor (LDLR) gene, which leads to the reduction or absence of cell surface LDLR, disorder of cholesterol metabolism, and cholesterol deposition in different tissues and organs. FH is a common metabolic disease clinically characterized by the presence of xanthomas and premature coronary heart disease. To date, about 1 741 variants have been identified in gene LDLR, among which 108 variants were identified in Chinese FH patients. To better understand the features of LDLR gene mutations and help to FH diagnosis and therapy, this review provides a comprehensive overview of LDLR gene mutations in Chinese FH patients.

参考文献

[1] Goldstein JL, Brown MS. The LDL Receptor. Arterioscler Thromb Vasc Biol, 2009, 29(4): 431–438.

[2] Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hy-percholesterolemia: A HuGE prevalence review. Am J Epidemiol, 2004, 160(5): 407–420.

[3] Hobbs HH, Russell DW, Brown MS, Goldstein JL. The LDL receptor locus in familial hypercholesterolemia: mu-tational analysis of a membrane protein. Annu Rev Genet, 1990, 24: 133–170.

[4] Ranheim T, Kulseth MA, Berge KE, Leren TP. Model system for phenotypic characterization of sequence varia-tions in the LDL receptor gene. Clin Chem, 2006, 52(8): 1469–1479.

[5] Neff D, Ruschitzka F, Hersberger M, Enseleit F, Hürlimann D, Noll G, Lüscher T, Hänseler E. Detection of a novel exon 4 low-density lipoprotein receptor gene dele- tion in a Swiss family with severe familial hypercho- les-terolemia. Clin Chem Lab Med, 2003, 41(3): 266–271.

[6] Chang JH, Pan JP, Tai DY, Huang AC, Li PH, Ho HL, Hsieh HL, Chou SC, Lin WL, Lo E, Chang CY, Tseng J, Su MT, Lee-Chen GJ. Identification and characterization of LDL receptor gene mutations in hyperlipidemic Chi-nese. J Lipid Res, 2003, 44(10): 1850–1858.

[7] Sun XM, Patel DD, Webb JC, Knight BL, Fan LM, Cai HJ, Soutar AK. Familial hypercholesterolemia in China. Iden-tification of mutations in the LDL-receptor gene that result in a receptor-negative phenotype. Arterioscler Thromb Vasc Biol, 1994, 14(1): 85–94.

[8] Hobbs HH, Brown MS, Goldstein JL. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Muta, 1992, 1(6): 445–466.

[9] 刘燕荣, 陶谦民, 陈君柱, 陶明, 郭晓纲, 尚云鹏, 朱建华, 张芙荣, 郑良荣, 王兴祥. 家族性高胆固醇血症患者低密度脂蛋白受体基因新突变位点的鉴定. 生理学报, 2004, 56(5): 566–572.

[10] Khoo KL, van Acker P, Defesche JC, Tan H, van de Kerkhof L, Heijnen-van Eijk SJ, Kastelein JJ, Deslypere JP. Low-density lipoprotein receptor gene mutations in a Southeast Asian population with familial hypercholes- terolemia. Clin Genet, 2000, 58(2): 98–105.

[11] Chiou KR, Charng MJ. Detection of mutations and large rearrangements of the low-density lipoprotein receptor gene in Taiwanese patients with familial hypercholes- terolemia. Am J Cardiol, 2010, 105(12): 1752–1758.

[12] Mak YT, Pang CP, Tomlinson B, Zhang J, Chan YS, Mak TW, Masarei JR. Mutations in the low-density lipoprotein receptor gene in Chinese familial hypercholesterolemia patients. Arterioscler Thromb Vasc Biol, 1998, 18(10): 1600–1605.

[13] 王燕飞, 金红芳, 卜定方, 杨艳玲, 杜军保. 家族性高胆固醇血症低密度脂蛋白受体基因新突变位点的鉴定——附1例报告. 中国实用内科杂志, 2008, 28(6): 450–452.

[14] Cheng XH, Zheng F, Zhou X, Xiong CL, Ding J, Chen YM. Mutation screening and functional analysis of low density lipoprotein receptor in a familial hypercholesterolemia family. Chin J Med Genet, 2008, 25(1): 55–58.

[15] 蔺洁, 王绿娅, 刘舒, 张红, 褚小玲, 潘晓冬, 杜兰平, 姜志胜. 家族性高胆固醇血症性黄瘤病LDL—R基因的突变. 中华皮肤科杂志, 2007, 40(12): 752–755.

[16] 王绿娅, 曹守春, 蔺洁, 吴邦俊, 刘舒, 潘晓冬, 杜兰平, 秦彦文, 陈保生. 家族性高胆固醇血症患者低密度脂蛋白受体基因复合纯合突变一例. 中华心血管病杂志, 2003, 31(9): 653–656.

[17] Pimstone SN, Sun XM, du Souich C, Frohlich JJ, Hayden MR, Soutar AK. Phenotypic variation in heterozygous fa-milial hypercholesterolemia: A comparison of Chinese pa-tients with the same or similar mutations in the LDL re-ceptor gene in China or Canada. Arterioscler Thromb Vasc Biol, 1998, 18(2): 309–315.

[18] Xie L, Gong QH, Xie ZG, Liang ZM, Hu ZM, Xia K, Xia JH, Yang YF. Two novel mutations of the LDL receptor gene associated with familial hypercholesterolemia in a Chinese family. Chin Med J, 2007, 120(19): 1694–1699.

[19] Chen K, Mu YM, Wang BA, Guo QH, Lu ZH, Dou JT, Lu JM. Two novel mutations 685del 1 and D129G in the low-density lipoprotein receptor gene in a compound het-erozygote Chinese family with fam
文章导航

/