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 amyloid beta, 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. Conclusion: the LOC387715/ARMS2 gene is expressed in the human brain and it may concur to the individual risk for AD.