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

抽动秽语综合征（GTS）以多运动抽搐和一次或多次发声抽搐为特征。GTS被认为是由遗传决定的，其传播方式为常染色体显性，外显率不完全。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的病因有关。我们对D2受体和D4受体基因位点的多态性标记可能参与GTS遗传病因的假设进行了研究。从7例患者和28例嗜睡患者的外周血淋巴细胞中分离DNA。通过聚合酶链反应扩增D2TaqIA、D2TaqIB多态位点和D2TaqIB胞质环区48碱基对2 ~ 8倍重复序列，并用TaqI限制性内切酶酶切（如TaqIA和B位点）。利用限制性片段长度多态性进行多态性鉴定。我们将GTS和嗜睡症的等位基因频率与先前报道的正常对照进行比较。GTS患者A1等位基因的频率为14%(2/14)，而正常对照组为40%(70/176)，嗜睡症患者为43%（24/56）。GTS患者B1等位基因的频率为14%(2/14)，而正常对照为22%(38/138)，嗜睡症患者为39%（22/56）。D4受体多态性标记的频率如下：GTS中C3等位基因占94% (1/16)，C5等位基因占6%(1/16)，而日本正常对照中C1为1%，C2为5%，C3为78%，C4为1%，C5为15%。由于GTS病例较少，我们无法统计分析GTS的等位基因分布是否与正常对照有显著差异。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.