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

抽动秽语综合征(GTS)是以多种运动和一种或多种发声痉挛为特征的疾病。GTS被认为是由遗传决定的，其传播方式是常染色体显性的不完全外显。这种综合征的成功治疗主要使用D2多巴胺能受体拮抗剂，如氟哌啶醇。但目前尚不清楚多巴胺能系统是否在某种程度上与GTS有关。我们开展了一项研究，以检验D2受体和D4受体基因座上的多态标记可能与GTS的遗传病因有关的假说。聚合酶链式反应扩增D4受体基因第三胞质环区D2TaqIA、D2TaqIB多态位点和48个碱基重复序列的2~8倍重复序列，并用TaqI酶切(TaqIA和B位点)。通过限制性内切酶片段长度多态性分析，比较GTS和HYS的等位基因频率与已报道的正常对照的等位基因频率。GTS组A1等位基因频率为14%(2/14)，正常对照组为40%(70/176)，胸大肌症组为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)，胸腺功能亢进症为39%(22/56)。D4受体多态标记频率：GTS组C3等位基因为94%(1/16)，GTS组为6%(1/16)，而日本正常对照组分别为C11%、C2 5%、C3 78%、C4 1%、C5 15%。由于GTS病例数量较少，我们无法对GTS的等位基因分布是否与正常对照有显著差异进行统计分析。我们计划收集更多的GTS患者。

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.