IS THE POLYMORPHIC MICROSATELLITE REPEAT OF THE DOPAMINE-BETA-HYDROXYLASE GENE ASSOCIATED WITH BIOCHEMICAL VARIABILITY OF THE CATECHOLAMINEPATHWAY IN SCHIZOPHRENIA

Six allelic fragments were typed by a polymerase chain reaction proces s with a pair of primers specific for a sequence containing the polymo rphic (GT)n repeat a microsatellite repent, in the human dopamine beta -hydroxylase (DBH) gene. Their frequencies in unrelated patients with schizophrenia were 0.003 (Al), 0.114 (A2), 0.343 (A3), 0.526 (A4), 0.0 06 (A5), and 0.009 (A6), and in unrelated control subjects, 0.012 (Al) , 0.086 (A2), 0.309 (A3), 0.574 (A4), 0.006 (A5), and 0.012 (A6). Krus kal-Wallis analysis revealed significant differences among the three g roups, the drug-free and drug-treated patients, and the control subjec ts, in serum DBH activity of the subjects whose genotype was A2/A3 (H = 6.0, p < .05) or A3/A3 (H = 9.8, p < .01), inserum homovnniliic acid concentration of those whose genotype was A3/A4 (H = 7.7, p <.025), a nd in serum tyrosine concentration of those whose genotype was A4/A4 ( H = 8.3, p < .02). Mann-Whitney U test showed that in the subjects car rying the A3/A4 genotype, serum noradrenaline concentration of drug-tr eated patients was significantly higher than that of control subjects (N = 58, p < .02). These results suggest that genotypic polymorphism o f the human DBH is likely to be associated with biochemical variabilit y of the catecholamine pathway in schizophrenia. (C) 1997 Society of B iological Psychiatry.