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Functional polymorphisms in the sigma1 receptor gene associated with alcoholism
Ryosuke Miyatake1, Aizo Furukawa, Sachio Matsushita
1Institute of Clinical Research, National Alcoholism Center Kurihama Hospital, Kanagawa, Japan.
Biological Psychiatry
|January 7, 2004
Summary
Genetic variations in the sigma1 receptor gene (SIGMAR1) may influence alcoholism susceptibility. Specific SIGMAR1 alleles and haplotypes appear to be protective factors against developing alcoholism.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Sigma1 receptors play a role in drug abuse pathogenesis.
- Two known polymorphisms (GC-241-240TT and Gln2Pro) exist in the sigma1 receptor gene (SIGMAR1).
Purpose of the Study:
- To investigate the role of SIGMAR1 gene polymorphisms in alcoholism susceptibility.
- To conduct a functional analysis and case-control study of SIGMAR1 variants.
Main Methods:
- Screening for polymorphisms in the 5'-upstream region of SIGMAR1.
- Assessing the impact of polymorphisms on transcriptional activity using a gene reporter assay.
- Analyzing the distribution of SIGMAR1 polymorphisms in alcoholic and control cohorts.
Main Results:
- A novel T-485A polymorphism was identified.
- The A-485 allele and TT-241-240 allele showed significantly reduced transcriptional activity.
- The A-485 allele and TT-241-240/Pro2 haplotype were more frequent in control subjects than alcoholic subjects.
Conclusions:
- The T-485A and GC-241-240TT polymorphisms are likely functional.
- The A-485 allele and TT-241-240/Pro2 haplotype may act as protective factors against alcoholism development.