Association study of dysbindin gene with clinical and outcome measures in a representative cohort of Italian schizophrenic patients.
There is evidence suggesting that Dysbindin (DTNBP1) is a susceptibility gene for schizophrenia in Caucasian, Chinese, and Japanese populations. We sought to determine if dysbindin was associated with schizophrenia and its symptoms in a representative group of schizophrenic patients from a Community-Based Mental Health Service (CMHS) in Verona, Italy. A prevalence cohort of schizophrenic patients (n = 141) was assessed at baseline and then 3 and 6 years later. Eighty patients and 106 healthy controls were genotyped for polymorphisms in dysbindin. We tested if diagnosis, clinical symptoms as measured by the Brief Psychiatric Rating Scale (BPRS), and functioning as measured by the Global Assessment of Functioning Scale (GAF), were associated with the presence of certain dysbindin polymorphisms. Finally, using the longitudinal clinical data, we tested if patients carrying dysbindin high-risk haplotypes had a more unfavorable longitudinal clinical outcome. A trend towards statistical association (P = 0.058) between schizophrenia and rs2619538 was found. Using GENECOUNTING software, we found that rs2619538-P1583 (P = 0.048), P1320-P1757 (P = 0.034), and rs2619538-P1583-P1578 (P = 0.040) haplotypes occurred more often in cases compared to controls before correction for multiple testing. The rs2619538-P1583 haplotype was more likely to be transmitted to subjects with more severe and persistent psychopathology. These preliminary results are compatible with the view that DTNBP1 is a susceptibility factor for schizophrenia, and is associated with worse psychopathology.
Tosato
Sarah
S
Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy. sarah.tosato@univr.it
Ruggeri
Mirella
M
Bonetto
Chiara
C
Bertani
Mariaelena
M
Marrella
Giovanna
G
Lasalvia
Antonio
A
Cristofalo
Doriana
D
Aprili
Giuseppe
G
Tansella
Michele
M
Dazzan
Paola
P
Diforti
Marta
M
Murray
Robin M
RM
Collier
David A
DA
D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007406:Interview, Psychological; D007558:Italy / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins