An intron 1 polymorphism in the cholecystokinin-A receptor gene associated with schizophrenia in males

TY - JOUR

T1 - An intron 1 polymorphism in the cholecystokinin-A receptor gene associated with schizophrenia in males

AU - Koefoed, P

AU - Hansen, T V O

AU - Woldbye, D P D

AU - Werge, T

AU - Mors, O

AU - Hansen, T

AU - Jakobsen, K D

AU - Nordentoft, M

AU - Wang, A

AU - Bolwig, T G

AU - Rehfeld, J F

AU - Koefoed, P

AU - Hansen, T V O

AU - Woldbye, D P D

AU - Werge, T

AU - Mors, O

AU - Hansen, Thomas Folkmann

AU - Jakobsen, Klaus Damgaard

AU - Nordentoft, M

AU - Wang, A

AU - Bolwig, T G

AU - Rehfeld, J F

N1 - Keywords: Adult; Case-Control Studies; Chromosomes, Human, Pair 4; Denmark; Diagnostic and Statistical Manual of Mental Disorders; Female; Gene Expression; Humans; International Classification of Diseases; Introns; Male; Polymorphism, Single Nucleotide; RNA Splice Sites; RNA, Messenger; Receptor, Cholecystokinin A; Schizophrenia; Severity of Illness Index; Sex Distribution

PY - 2009

Y1 - 2009

N2 - 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. METhod: 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. CONCLUSION: 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.

AB - 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. METhod: 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. CONCLUSION: 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.

M3 - Journal article

SN - 0001-690X

VL - 120

SP - 281

EP - 287

JO - Acta Psychiatrica Scandinavica

JF - Acta Psychiatrica Scandinavica

IS - 4

ER -