FAILURE TO REPLICATE AN ASSOCIATION BETWEEN A RARE ALLELE OF A TYROSINE-HYDROXYLASE GENE MICROSATELLITE AND SCHIZOPHRENIA

An association between schizophrenia and a rare perfect ten-repeat all ele, K1(p), of a tetranucleotide microsatellite polymorphism in the ty rosine hydroxylase gene has recently been reported. The rare allele wa s found only in schizophrenic patients. During treatment with antipsyc hotic drugs patients with the rare allele displayed lower plasma homov anillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels t han those without. We examined Swedish schizophrenic patients (n = 117 ) and healthy control subjects (n = 76) for the same polymorphism. In contrast to the previous studies, the K1(p) frequency in patients (4 o f 117) tended to be lower than among controls (9 of 76). With all six alleles (K1(p), K1(i), K2-5) considered there was a significant differ ence between schizophrenic patients and control subjects. There was no significant difference in HVA and MHPG levels in cerebrospinal fluid from a subset (n = 64) of control subjects with and without the rare a llele. The discrepant results warrant further investigation of the tyr osine hydroxylase gene.