CBS GENE IN HOMOCYSTINURIA AND ARTERIOSCLEROSIS

同型半胱氨酸尿症和动脉硬化中的 CBS 基因

• 批准号: 6188777
• 负责人: JAN P. KRAUS
• 金额: $ 3.15万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6188777
• 关键词: arteriosclerosis; blood chemistry; clinical research; cystathionine beta synthase; enzyme induction /repression; fibroblasts; gene expression; gene mutation; genetic polymorphism; homocystinuria; human subject; inborn metabolism disorder diagnosis; tissue /cell culture

DESCRIPTION: The parent grant has its aims the elucidation of genetic, biochemical and pathogenetic aspects of metabolic disorders resulting in mental retardation (Stephen Goodman, P.I.). The applicant (Jan P. Kraus, Ph.D.) us a Project Leader in this program project grant and has developed this application to collaborate with Viktor Kozich, M.D., Ph.D. from Charles University in Prague, Czech Republic. The applicant proposes to determine the mechanisms of altered gene expression of the cystathionine b-synthase (CBS) gene in classical Homocystinuria (related to the Parent Grant) and also in patients with coronary/peripheral arterial disease (Homocysteine metabolism and atherosclerosis) in whom a mild hyperhomocystinemia is present. The purpose of the investigation is to define the molecular events related to the CBS gene that may be relevant to efficient diagnosis and treatment of these disorders. The applicant is focusing on the role of a frequent (5-9% of the population) polymorphism (844ins68bp allele in the CBS gene) with respect to the incidence of homocystinuria, the possible role of this allele in inducing a common mutation(1278T) that may also explain the incidence of disease and the impact of the allele mutation on the steady state of normal CBSmRNA in cultured fibroblasts. An extensive analysis of the mutations in the CBS gene will be evaluated from blood samples of patients with homocystinuria from abroad ad mutations have been shown to be differently distributed in various populations. Finally the applicant proposes to study how the mutations in regulatory portions of the CBS gene may have caused the low CBS expression leading to abnormal homocysteine metabolism.

产品说明： 父母补助金的目的是阐明遗传、生化和 代谢紊乱导致精神 （Stephen Goodman，P.I.）。申请人（Jan P. Kraus，Ph.D.） 我们是这个项目的项目负责人，并开发了这个 申请与Viktor Kozich，M.D.，博士于查理 捷克共和国布拉格的大学。申请人建议确定 胱硫醚B合酶基因表达改变的机制 (CBS)经典同型胱氨酸尿症中的基因（与父母补助金有关）， 在患有冠状动脉/外周动脉疾病的患者中（同型半胱氨酸 代谢和动脉粥样硬化），其中轻度高同型半胱氨酸血症是 礼物调查的目的是确定分子 可能与有效诊断相关的CBS基因相关事件 和治疗这些疾病。申请人侧重于以下方面的作用： 一个常见的（5-9%的人群）多态性（844 ins 68 bp等位基因在 CBS基因）与同型胱氨酸尿症的发生率有关， 该等位基因在诱导一种常见突变（1278 T）中的作用， 解释疾病的发生率和等位基因突变对 正常CBSmRNA在培养的成纤维细胞中的稳定状态。一个广泛 CBS基因突变的分析将从血液中进行评估 从国外收集的同型胱氨酸尿症患者的样本， 在不同的人群中分布不同。最后 申请人建议研究如何在调控部分的突变， CBS基因可能导致CBS表达降低，导致异常的 同型半胱氨酸代谢

项目成果

Diversity of cystathionine beta-synthase haplotypes bearing the most common homocystinuria mutation c.833T>C: a possible role for gene conversion.

具有最常见同型半胱氨酸尿症突变 c.833T>C 的胱硫醚β-合酶单倍型的多样性：基因转换的可能作用。

• DOI: 10.1002/humu.20430
• 发表时间: 2007
• 期刊: Human mutation
• 影响因子: 3.9
• 作者: Vyletal,Petr;Sokolová,Jitka;Cooper,DavidN;Kraus,JanP;Krawczak,Michael;Pepe,Guglielmina;Rickards,Olga;Koch,HansG;Linnebank,Michael;Kluijtmans,LeoAJ;Blom,HenkJ;Boers,GodfriedHJ;Gaustadnes,Mette;Skovby,Flemming;Wilcken,Br
• 通讯作者: Wilcken,Br

Haplotyping of wild type and I278T alleles of the human cystathionine beta-synthase gene based on a cluster of novel SNPs in IVS12.

• DOI: 10.1002/humu.36
• 发表时间: 2001-04-01
• 期刊: Human mutation
• 影响因子: 3.9
• 作者: Linnebank, M;Homberger, A;Koch, H G
• 通讯作者: Koch, H G