Polymorphisms in the LOC387715/ARMS2 putative gene and the risk for Alzheimer's disease.
BACKGROUND
Age-related macular degeneration (ARMD) and Alzheimer's disease (AD) are neurodegenerative disorders that share a high prevalence among elderly people, the extracellular deposition of beta-amyloid and the involvement of genetic factors in their aetiology. Genetic linkage with the chromosome regions 10q26 and 10q24-25 have been shown for ARMD and AD, respectively. The rs10490924 polymorphism, the major determinant of the 10q26 association with ARMD, determines the A69S substitution in the LOC387715/ARMS2 gene. Little information is available about the expression of the gene in humans.


METHODS
We analysed the expression of the gene by RT-PCR in the brain and we looked for nucleotide variations in the gene sequence by DHPLC.


RESULTS
We found specific gene transcripts in the hippocampus, cortex and cerebellum. The genetic analysis identified two other common variations, which determine the R3H change (rs10490923) and a premature stop codon (rs2736911), respectively. The analysis of their distribution in 213 AD patients and 149 controls revealed a trend for a reduced frequency of the variant allele of rs2736911 in AD patients (p = 0.038), with an odds ratio of 0.631.


CONCLUSIONS
The LOC387715/ARMS2 gene is expressed in the human brain, and it may concur to the individual risk for AD.
Gatta
Luisa Benerini
LB
Section of Biochemistry, Faculty of Medicine, University of Brescia, Brescia, Italy.
Vitali
Massimiliano
M
Zanola
Alessandra
A
Venturelli
Eliana
E
Fenoglio
Chiara
C
Galimberti
Daniela
D
Scarpini
Elio
E
Finazzi
Dario
D
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
C514392:ARMS2 protein, human; D053327:Apolipoprotein E4; D011506:Proteins