Polymorphisms of the CCK, CCKAR and CCKBR genes: an association with alcoholism study.
OBJECTIVE
Cholecystokinin (CCK) plays an important role in the functioning of the central nervous system via an interaction with dopamine and other neurotransmitters. The dopaminergic system has been implicated in the maladaptive behaviors associated with drugs of abuse (e.g., alcohol and cocaine). We analyzed genetic variations in the promoter and coding regions of the CCK, CCKA-receptor (CCKAR) and CCKB-receptor (CCKBR) genes, and performed association analyses with alcoholism.


METHODS
A total of 214 Japanese male patients with alcoholism (93 with delirium tremens, 49 with hallucinations, 38 with seizures and 83 without any of these symptoms) and 98 age-matched Japanese male controls were examined using PCR-based Single Strand Conformational Polymorphism (SSCP) analysis.


RESULTS
A total of 8 variants in the CCK gene, 11 variants in the CCKAR gene and 9 variants in the CCKBR gene were detected in the present study. Nominally significant differences between alcoholics and controls were found at the -85 locus of the CCKAR gene (p = .035). In addition, patients displaying hallucinations showed a higher frequency of the homozygous genotype of the allele (GT)8 at the -388 locus of the CCKAR gene (p = .042) and homo- and heterozygous genotypes of the T allele at the -333 locus (p = .025), relative to other patients. However, these differences were not significant after Bonferroni correction.


CONCLUSIONS
Our data suggest that polymorphisms of the CCK, CCKAR and CCKBR genes do not play a major role in alcohol withdrawal symptoms (even though significant associations were found among polymorphisms at the -388 and -333 loci of the CCKAR gene and hallucinations, the rate was nonsignificant after Bonferroni correction).
Okubo
T
T
Department of Environmental Ecosystem, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
Harada
S
S
D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002766:Cholecystokinin / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004587:Electrophoresis, Agar Gel / Q000379:methods; D000431:Ethanol / Q000009:adverse effects; D005091:Exons / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis
D017931:DNA Primers; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D000431:Ethanol; D002766:Cholecystokinin; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial