Dopamine beta-hydroxylase (DBH) gene and schizophrenia phenotypic variability: a genetic association study.
Recently, two polymorphisms (DBH5'-Ins/del and DBH 444 g/a) of the Dopamine Beta Hydroxylase (DBH) gene were isolated, and one haplotype (Del-a) was found to be associated with low DBH activity and cocaine-induced paranoia. The purpose of this study is to test for association between these two polymorphisms and schizophrenia or its phenotypic variability with respect to neuroleptic therapeutic response and symptom profile. Allelic and haplotype distributions of these two polymorphisms were compared between two groups of schizophrenic patients (excellent neuroleptic-responders; R, n = 42 and non-responders; NR, n = 64), and one group of healthy volunteers (n = 120). The "Del" and "a" alleles were in positive linkage disequilibrium. No allelic or genotype differences in the distribution of these two polymorphisms were observed between patients and controls. However, The Del-a haplotype was significantly more common in NR patients, and the mean total BPRS score was significantly higher in the group of patients with the Del-a compared to those without the Del-a haplotype. These results suggest that the DBH gene is not a causative factor in schizophrenia but that it may be a modulator of psychotic symptoms, severity of the disorder and therapeutic response to neuroleptic drugs.
Yamamoto
Kenji
K
Douglas Hospital Research Centre; 6875 Boulevard LaSalle, Verdun H4H 1R3, Canada.
Cubells
Joseph F
JF
Gelernter
Joel
J
Benkelfat
Chawki
C
Lalonde
Pierre
P
Bloom
David
D
Lal
Samarthji
S
Labelle
Alain
A
Turecki
Gustavo
G
Rouleau
Guy A
GA
Joober
Ridha
R
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D016022:Case-Control Studies; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics*
D014150:Antipsychotic Agents; D004299:Dopamine beta-Hydroxylase