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 + 121 C/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 + 121 G and + 121 C alleles of this SNP. Further investigations revealed two risk haplotypes: + 121 C/ + 978A/ + 984T (P = 0.01) and + 121 C/ + 978T/ + 984C (P = 0.0091) as well as a protective haplotype: + 121G/ + 978T/ + 984T (P = 0.0001). Conclusion: 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.