Analysis of Dopamime D2 receptor gene in Gilles de la Tourette syndrome

抽动秽语综合征多巴胺D2受体基因分析

• 批准号: 07671049
• 负责人: FUKUDA Masato
• 金额: $ 1.09万
• 依托单位: UNIVERSITY of TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671049/
• 关键词: Gilles de la Tourette syndrome; dopamime; D2 receptor; D4 receptor; genetic polymorphism; RFLP; D2受容体; D4受容体; 遺伝子

Gilles de la Tourette syndrome (GTS) is characterized by multiple motor and one or more vocal tics. GTS is thought to be genetically determined with the mode of transmission being autosomal dominant with incomplete penetrance. Successful treatment of this syndrome employ predominantly D2 dopaminergic receptor antagonists such as haloperidol. But it is not clear whether the dopaminergic system is in some way etiologically responsible for GTS.We have carried out research to test the hypothesis that polymorphic markers within D2 receptor and D4 receptor gene loci may contribute to the genetic etiology of GTS.DNA was isolated from peripheral lymphocytes of 7 patients and 28 hypersomiacs. D2TaqIA,D2TaqIB polymorphic sites and two-to eight-fold repeats of 48-base-pair sequence in the putative third cytoplasmic loop region of D4 receptor gene were amplified by means of the polymerase chain reaction, and digested with TaqI restriction enzyme (as to TaqIA and B sites). The polymorphism were identified by the restriction fragment length polymorphism.We compare allele frequency of GTS and hypersomias with that of normal controls previously reported. The frequency of the A1 allele in GTS was 14% (2/14), compared to 40% (70/176) frequency of normal controls and 43% (24/56) frequency of hypersominas. The frequency of the B1 allele in GTS was 14% (2/14), whereas 22% (38/138) frequency of normal controls and 39% (22/56) frequency of hypersominas. The frequnecy of D4 receptor polymorphic markers were as follows ; C3 allele in GTS was 94% (1/16) and C5 allele in GTS was 6% (1/16), compared to C1 1%, C2 5%, C3 78%, C4 1%, C5 15% in normal Japanese controls. We cannnot perform the statistical analysis whether allelleic distributions of GTS were significantly differnt from normal controls, because oft he small number of GTS cases. We are planning to collect more patients with GTS.

抽动-秽语综合征（GTS）的特征是多个运动和一个或多个发声抽搐。GTS被认为是由遗传决定的，传播方式为常染色体显性遗传，不完全遗传。这种综合征的成功治疗主要采用D2多巴胺能受体拮抗剂，如氟哌啶醇。为验证D_2受体和D_4受体基因多态性可能与GTS的遗传病因有关的假说，我们从7例GTS患者和28例失眠症患者的外周血淋巴细胞中提取了DNA。用聚合酶链反应扩增D4受体基因第三胞质环区的D2 TaqIA、D2 TaqIB多态性位点和48个碱基对的2 ~ 8倍重复序列，用TaqI限制性内切酶（TaqIA和B位点）消化。采用限制性片段长度多态性分析方法，对GTS和多体症患者的等位基因频率进行分析，并与以往报道的正常对照组进行比较。GTS组A1等位基因频率为14%（2/14），正常对照组为40%（70/176），高血压组为43%（24/56）。GTS组B1等位基因频率为14%（2/14），正常对照组为22%（38/138），高血压组为39%（22/56）。D4受体多态性标记频率：GTS组C3等位基因频率为94%（1/16），C5等位基因频率为6%（1/16），而日本正常对照组C1 1%、C2 5%、C3 78%、C4 1%、C5 15%。由于GTS病例数较少，我们无法对GTS的等位基因分布是否与正常对照组有显著性差异进行统计分析。我们计划收集更多GTS患者。