Association study of structural mutations of the tyrosine hydroxylase gene with schizophrenia and Parkinson's disease

Tyrosine hydroxylase (TH) gene is the rate-limiting enzyme in the synthesis of catecholamines, Functional polymorphisms of the TH gene may be involved in the pathogenesis of neuropsychiatric diseases such as schizophrenia, affective disorders, and Parkinsonism. This study examined a possible association of two polymorphisms, both of which result in an amino acid change of the TH protein, with schizophrenia and Parkinson's disease (PD), The Val(81)Met polymorphism is a common variation, although its effect on the enzyme expression is unclear. Leu(205)Pro polymorphism is a rare mutation that is reported to cause Parkinsonism in infancy for individuals who are homozygous for the mutated type. We genotyped a Japanese sample of 194 schizophrenics, 99 patients with PD, and 161 controls for the Val(81)Met polymorphism by using mis-match PCR and digestion by the restriction enzyme Ball, There was no significant allelic or genotypic association of the Val(81)Met polymorphism with schizophrenia or PD, The Leu(205)Pro polymorphism was examined by using PCR and digestion by AluI; however, there was no individual who carried the mutated type of Pro(205) among 50 schizophrenics or 50 patients with PD. Thus we obtained no evidence for the involvement of the two structural mutations of the TH gene in the pathogenesis of schizophrenia or PD, (C) 1998 Wiley-Liss, Inc.