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Uchida, N. et al.

A variant of the sigma receptor type-1 gene is a protective factor for Alzheimer disease.

OBJECTIVE: Some preclinical evidence suggests that the sigma receptor type 1, which plays several roles in learning and memory, may also be involved in the pathogenesis of Alzheimer disease (AD). The authors provide here genetic evidence that the sigma receptor type 1 (SIGMAR1) gene is involved in susceptibility to AD. METHODS: Two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Q2P, were analyzed in a Japanese sample of 239 patients with AD and 227 comparisons subjects. These two polymorphisms were in complete linkage disequilibrium with each other, resulting in only two haplotypes, GC-241-240Q2 and TT-241-240P2. RESULTS: There was a significant association between AD and the TT-241-240P2 haplotype of the SIGMAR1 gene and its homozygote, found with late-onset, but not early-onset AD. After stratification by epsilon4 allele status of the apolipoprotein E gene, TT-241-240P2 homozygosity of the SIGMAR1 gene reduced the risk of AD in epsilon4 allele carriers by three-fourths. CONCLUSION: The present study suggests that the TT-241-240P2 haplotype of the SIGMAR1 gene, which decreases expression of the gene, may have a protective role against susceptibility to AD.[1]

References

A variant of the sigma receptor type-1 gene is a protective factor for Alzheimer disease. Uchida, N., Ujike, H., Tanaka, Y., Sakai, A., Yamamoto, M., Fujisawa, Y., Kanzaki, A., Kuroda, S. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. (2005) [Pubmed]

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