Association between CCK-AR gene and schizophrenia with auditory hallucinations.
OBJECTIVE
Previous studies on a possible association between CCK-AR polymorphisms and schizophrenia have been controversial. The aim of the present study was to assess a potential association between schizophrenic patients with auditory hallucinations and polymorphisms of the CCK-AR gene.


METHODS
A set of single nucleotide polymorphisms mainly located in the regulatory region of the CCK-AR gene was analysed in a sample of 163 Diagnostic and statistical manual of mental disorders-IV-diagnosed schizophrenic patients and 162 healthy controls.


RESULTS
Significant differences in the genotype (P=0.011) and allele (P=0.0009) frequencies of the +121C/G SNP (located in the 5' regulatory region) were found between patients and controls. The excess of the C allele in the patient group remained significant after Bonferroni correction (P=0.03). However, functional in vitro assays, did not reveal significant differences on gene expression between +121G and +121C alleles of this SNP. Further investigations revealed two risk haplotypes: +121C/+978A/+984T (P=0.01) and +121C/+978T/+984C (P=0.0091) as well as a protective haplotype: +121G/+978T/+984T (P=0.0001).


CONCLUSIONS
Our data support a possible role of the CCK-AR gene in the vulnerability to schizophrenia in patients with auditory hallucinations, and suggest remarkable allele heterogeneity.
Toirac
Ivette
I
Department of Genetics, University of Valencia, 46100, Burjassot, Valencia, Spain.
Sanjuán
Julio
J
Aguilar
Eduardo J
EJ
González
Jose C
JC
Artigas
Francesc
F
Rivero
Olga
O
Nájera
Carmen
C
Moltó
Maria D
MD
de Frutos
Rosa
R
D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D005787:Gene Frequency; D005838:Genotype; D006212:Hallucinations / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D043886:Receptor, Cholecystokinin A / Q000235:genetics*; D012016:Reference Values; D012045:Regulatory Sequences, Nucleic Acid; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology
D017931:DNA Primers; D043886:Receptor, Cholecystokinin A; D004247:DNA