An intron 1 polymorphism in the   cholecystokinin-A receptor gene associated   with schizophrenia in males.
OBJECTIVE
To identify whether a genetic variation (rs1800857; IVS1-5T>C) in the neuropeptide cholecystokinin-A receptor (CCKAR) gene is a risk factor in the pathogenesis of schizophrenia.


METHODS
The variation was analysed in a case-control design comprising 508 patients with schizophrenia and 1619 control subjects. A possible functional impact of this variant on CCKAR protein synthesis through alterations in splicing was analysed in an exon-trapping assay.


RESULTS
In males only, the risk variant, IVS1-5C, was associated with a significantly increased risk of schizophrenia. Carrying one risk allele was associated with an increased risk of 1.74 (Odds Ratio, OR) and homozygosity (CC) was associated with an OR of 3.19. The variation had no impact on protein synthesis of CCKAR.


CONCLUSIONS
This is the first report associating the CCKAR gene variant with schizophrenia specifically in men. Our study strengthens the conclusion that a CCKAR dysfunction could be involved in the aetiology of schizophrenia.
Koefoed
P
P
Department of Neuroscience and Pharmacology, Laboratory for Neuropsychiatry, University of Copenhagen & Centre of Psychiatry, Rigshospitalet, Denmark. pkoefoed@sund.ku.dk
Hansen
T V O
TV
Woldbye
D P D
DP
Werge
T
T
Mors
O
O
Hansen
T
T
Jakobsen
K D
KD
Nordentoft
M
M
Wang
A
A
Bolwig
T G
TG
Rehfeld
J F
JF
D000328:Adult; D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D038801:International Classification of Diseases; D007438:Introns / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D043886:Receptor, Cholecystokinin A / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D012720:Severity of Illness Index; D017678:Sex Distribution
D022821:RNA Splice Sites; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A