Functional polymorphisms in the sigma1 receptor gene associated with alcoholism
| Autor: | Susumu Higuchi, Aizo Furukawa, Sachio Matsushita, Hiroshi Suwaki, Ryosuke Miyatake |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Genotype Transcription Genetic Gene Expression Biology Personality Disorders Severity of Illness Index Gene Frequency Japan Gene expression Humans Receptors sigma Genetic Predisposition to Disease Allele Gene Biological Psychiatry ALDH2 Genetics Reporter gene Polymorphism Genetic Aldehyde Dehydrogenase Mitochondrial Haplotype Case-control study Aldehyde Dehydrogenase Diagnostic and Statistical Manual of Mental Disorders Hospitalization Alcoholism Haplotypes Case-Control Studies |
| Zdroj: | Biological Psychiatry. 55:85-90 |
| ISSN: | 0006-3223 |
| Popis: | Sigma1 receptors are involved in the pathogenesis of drug abuse. Two polymorphisms (GC-241-240TT and Gln2Pro) in the sigma1 receptor gene (SIGMAR1) have been identified. To investigate the role of SIGMAR1 in conveying susceptibility to alcoholism, we performed a functional analysis of polymorphisms in the SIGMAR1 and a case-control study.We initially screened for polymorphisms in the 5'-upstream region. The effects of the polymorphisms on transcriptional activity were determined using a gene reporter assay. The distribution of SIGMAR1 polymorphisms was analyzed in 307 alcoholic and 302 control subjects.A novel T-485A polymorphism was identified. The transcriptional activity of the A-485 allele and the TT-241-240 allele was significantly reduced compared with that of the T-485 allele and the GC-241-240 allele. The frequencies of the A-485 allele (chi2=5.575, df=1, p=.0205) and the TT-241-240/Pro2 haplotype (chi2=21.464, df=1, p.0001) were significantly higher in control subjects compared with alcoholic subjects. The T-485A and the GC-241-240TT may be functional polymorphisms, and the A-485 allele and TT-241-240/Pro2 haplotype are possible protective factors for the development of alcoholism. |
| Databáze: | OpenAIRE |
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