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

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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.