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.


CONCLUSIONS
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.
Uchida
Naohiko
N
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
Ujike
Hiroshi
H
Tanaka
Yuji
Y
Sakai
Ayumu
A
Yamamoto
Mitsutoshi
M
Fujisawa
Yoshikatsu
Y
Kanzaki
Akihiro
A
Kuroda
Shigetoshi
S
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D015536:Down-Regulation; D005091:Exons / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017480:Receptors, sigma / Q000235:genetics*
D012333:RNA, Messenger; D017480:Receptors, sigma