Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction.
Recent reports indicate that DAO, DAOA, DTNBP1, NRG1 and RGS4 are some of the most-replicated genes implicated in susceptibility to schizophrenia. Also, the functions of these genes could converge in a common pathway of glutamate metabolism. The aim of this study was to evaluate if each of these genes, or their interaction, was associated with schizophrenia. A case-control study was conducted in 589 Spanish patients having a diagnosis of schizophrenia, and compared with 617 equivalent control subjects. Several single nucleotide polymorphisms (SNPs) in each gene were determined in all individuals. SNP and haplotype frequencies were compared between cases and controls. The interaction between different SNPs at the same, or at different gene, loci was analyzed by the multifactor dimensionality reduction (MDR) method. We found a new schizophrenia risk and protective haplotypes in intron VII of DTNBP1; one of the most important candidate genes for this disorder, to-date. However, no association was found between DAO, DAOA, NRG1 and RGS4 and schizophrenia. The hypothesis that gene-gene interaction in these five genes could increase the risk for the disorder was not confirmed in the present study. In summary, these results may provide further support for an association between the dysbindin gene (DTNBP1) and schizophrenia, but not between the disease and DAO, DAOA, NRG1 and RGS4 or with the interaction of these genes. In the light of recent data, these results need to be interpreted with caution and future analyses with dense genetic maps are awaited.
Vilella
Elisabet
E
Faculty of Medicine, Rovira i Virgili University, Reus, Spain. elisabet.vilella@urv.cat
Costas
Javier
J
Sanjuan
Julio
J
Guitart
Míriam
M
De Diego
Yolanda
Y
Carracedo
Angel
A
Martorell
Lourdes
L
Valero
Joaquín
J
Labad
Antonio
A
De Frutos
Rosa
R
Nájera
Carmen
C
Moltó
M Dolores
MD
Toirac
Ivette
I
Guillamat
Roser
R
Brunet
Anna
A
Vallès
Vicenç
V
Pérez
Lucía
L
Leon
Melquíades
M
de Fonseca
Fernando Rodríguez
FR
Phillips
Christopher
C
Torres
María
M
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D023281:Genomics / Q000379:methods; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D047668:Inteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020710:RGS Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D002352:Carrier Proteins; C475071:DAOA protein, human; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D047908:Intracellular Signaling Peptides and Proteins; C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D020710:RGS Proteins; D011956:Receptors, Cell Surface; C087452:diamine oxidase receptor, human; C098799:RGS4 protein