Is the polymorphic microsatellite repeat of the dopamine beta-hydroxylase gene associated with biochemical variability of the catecholamine pathway in schizophrenia?
Six allelic fragments were typed by a polymerase chain reaction process with a pair of primers specific for a sequence containing the polymorphic (GT)n repeat, a microsatellite repeat, in the human dopamine beta-hydroxylase (DBH) gene. Their frequencies in unrelated patients with schizophrenia were 0.003 (A1), 0.114 (A2), 0.343 (A3), 0.526 (A4), 0.006 (A5), and 0.009 (A6), and in unrelated control subjects, 0.012 (A1), 0.086 (A2), 0.309 (A3), 0.574 (A4), 0.006 (A5), and 0.012 (A6). Kruskal-Wallis analysis revealed significant differences among the three groups, the drug-free and drug-treated patients, and the control subjects, 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), in serum homovanillic acid concentration of those whose genotype was A3/A4 (H = 7.7, p < .025), and 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 carrying the A3/A4 genotype, serum noradrenaline concentration of drug-treated patients was significantly higher than that of control subjects (N = 58, p < .02). These results suggest that genotypic polymorphism of the human DBH is likely to be associated with biochemical variability of the catecholamine pathway in schizophrenia.
Wei
J
J
Institute of Biological Psychiatry, Schizophrenia Association of Great Britain, Bangor, Gwynedd, United Kingdom.
Xu
H M
HM
Ramchand
C N
CN
Hemmings
G P
GP
D000328:Adult; D000483:Alleles; D001921:Brain / Q000503:physiopathology; D002395:Catecholamines / Q000502:physiology*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology
D002395:Catecholamines; D004299:Dopamine beta-Hydroxylase