An association of the polymorphic repeat of tetranucleotide (TCAT) in the first intron of the human tyrosine hydroxylase gene with schizophrenia in a Japanese sample

Tyrosine hydroxylase (TH) is the rate limiting enzyme in the synthesis of dopamine and norepinephrine. A polymorphic repeat of the tetranucleotide (TCAT) in the first intron of the TH gene may behave as a regulatory element for the gene expression. Allelic fragments of the tandem repeat were typed by a PCR-based process with a pair of primers specific for the polymorphic sequence. The association between the polymorphism and schizophrenia was examined in a Japanese sample. There was a statistically significant association between the polymorphism and schizophrenia in females (χ2 = 26.018, p = 0.010), but not in males (χ2 = 15.995, p = 0.305). The genotype heterozygous for the TH9 and TH6 was significantly decreased in female schizophrenics (χ2 = 5.125, p = 0.0236). These results suggest that TH could be considered as a minor gene contributing to the susceptibility of Japanese female schizophrenia.