遗传 ›› 2013, Vol. 35 ›› Issue (11): 1237-1243.doi: 10.3724/SP.J.1005.2013.01237

• 综述 •    下一篇

血脂异常遗传性疾病的研究现状

何轶群1,2, 许美芬1,2, 于涵1,2, 耿军伟1,2, 施苏雪1,2, 薛凌1,2, 卢中秋3, 管敏鑫1,2,4   

  1. 1. 温州医学院Attardi线粒体生物医学研究院, 温州 325035; 
    2. 温州医学院浙江省医学遗传学重点实验室, 温州 325035; 
    3. 温州医学院附属第一医院急救医疗室, 温州 325000; 
    4. 浙江大学生命科学学院, 杭州 310058
  • 收稿日期:2013-03-24 修回日期:2013-05-16 出版日期:2013-11-20 发布日期:2013-10-25
  • 通讯作者: 管敏鑫, 教授, 博士生导师, 研究方向:人类遗传学。 E-mail:gminxin88@gmail.com
  • 作者简介:何轶群, 在读硕士研究生, 专业方向:分子诊断学。Tel: 18267729668; E-mail: hyq3375@163.com
  • 基金资助:

    卫生部科学研究基金-浙江省医药卫生重大科技计划项目(编号:WKJ2011-2-011)和温州市科技局重大项目(编号:H20100077)资助

Research progress in heritable dyslipidemia

HE Yi-Qun1,2, XU Mei-Fen1,2, YU Han1,2, GENG Jun-Wei1,2, SHI Su-Xue1,2, XUE Ling1,2, LU Zhong-Qiu3, GUAN Min-Xin1,2,4   

  1. 1. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou 325035, China; 
    2. Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou 325035, China; 
    3. Emergercy Medical Department, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China; 
    4. College of Life Sciences, Zhejiang University, Hangzhou 310058, China
  • Received:2013-03-24 Revised:2013-05-16 Online:2013-11-20 Published:2013-10-25

摘要:

血脂异常(Dyslipidemia)是指血浆中胆固醇和(或)甘油三酯水平升高, 可导致严重的心血管疾病, 常以冠心病和脑中风为首发表现, 该类疾病严重危害着人们的健康。一些血脂异常疾病具有遗传性, 主要包括孟德尔遗传和多基因遗传。传统检测血脂异常相关基因的方法主要有DNA测序和连锁分析, 适合于孟德尔遗传性血脂异常疾病。最近几年兴起的新一代测序技术(Next-generation sequencing)不仅适用于孟德尔遗传性血脂异常疾病的研究, 同样适用于复杂性血脂异常疾病。2006年至今, 运用全基因组关联分析(Genome wide association study, GWAS)筛出许多与血脂异常疾病相关的基因, 这些基因和早期孟德尔遗传家系确定的基因多数相同。GWAS频谱分析发现, 复杂性疾病相关的基因变异频率存在差异, 并且几乎所有筛查出的与血脂异常疾病相关的单核苷酸多态性(Single nucleotide polymorphisms, SNPs)变异均位于非编码区, 使得人们逐渐对非编码区基因变异展开了研究。血脂异常致病基因的发现和基因变异致病机制的阐明, 为血脂异常疾病提供新的治疗靶点, 并为新一代药物筛选提供新思路。文章对血脂异常遗传性疾病的研究现状进行了综述。

关键词: 血脂异常, 孟德尔遗传, 多基因遗传, 基因突变, 致病基因

Abstract:

Dyslipidemia is defined as high levels of serum cholesterol and/or triglycerides. Dyslipidemia often leads to severe cardiovascular diseases including coronary heart disease and stroke as the first clinical manifestation, thus threatening the health of human beings. Dyslipidemia diseases can be caused by the genetic factors, including the Mandelian or polygenic inheritance. Traditional methods of identifying genes associated with dyslipidemia are mainly DNA sequencing and linkage analysis, suitable for Mendelian genetic dyslipidemia disease. The rise of next-generation sequencing technology applies to not only Mandelian inheritance, but also complex forms of dyslipidemia diseases. Since 2006, genome-wide association studies (GWAS) screened out many causative genes associated with dyslipidemia, and most of these genes were the previously identified ones by the pedigree-based classic approaches. Furthermore, GWAS revealed that there were the different frequencies of gene variations related to complex forms of dyslipidemia diseases. Most of the identified single nucleotide polymorphisms (SNPs) associated with dyslipidemia are located in non-coding regions and thus people gradually focus on the gene variations of these loci. The identification of the causative genes will provide new insights into the pathophysiology of dyslipidemia diseases and a step toward therapeutic intervention. This review summarized recent pro-gress in heritable dyslipidemia.

Key words: dyslipidemia, Mendelian inheritance, polygenic inheritance, gene mutation, causative gene