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.

Gilles de la Tourette综合征（GTS）的特征是多发电动机和一种或多种声乐。 GTS被认为是遗传确定的，其传播方式是常染色体显性，而渗透不完全。该综合征的成功治疗主要采用D2多巴胺能受体拮抗剂，例如氟哌啶醇。但是，尚不清楚多巴胺能系统是否以某种方式对GTS.进行病因，我们已经进行了研究以检验以下假设：D2受体和D4受体基因位点内的多态性标记物可能有助于GTS.DNA的遗传学学病因，从外围淋巴细胞的遗传学病因中分离出来。 D2TAQIA，D2TAQIB多态位点和在假定的第三个基因的第三个基因的细胞质环中的48个基本对序列的两到八倍重复序列通过聚合酶链链反应进行扩增，并用Taqi限制性enzyme（如Taqi enzyme（如Taqi and to Taqia and Bere）消化）。通过限制片段长度多态性确定了多态性。我们比较GTS和高血压的等位基因频率与先前报道的正常对照组的等位基因频率。 GTS中A1等位基因的频率为14％（2/14），而正常对照的频率为40％（70/176），而Hypersominas的频率为43％（24/56）。 GTS中B1等位基因的频率为14％（2/14），而正常对照的频率为22％（38/138）和Hypersominas的39％（22/56）频率。 D4受体多态性标记的Frequnecy如下。 GTS中的C3等位基因为94％（1/16），GTS中的C5等位基因为6％（1/16），而日本正常对照组中的C1 1％，C2 5％，C3 78％，C4 1％，C4 1％，C5 15％。我们插入了统计分析，因为GTS的少数GTS病例，GTS的等位基因分布是否与正常对照组有显着差异。我们计划收集更多GTS患者。