Polymorphisms in the LOC387715/ARMS2 putative gene and the risk for Alzheimer's disease

Dement Geriatr Cogn Disord. 2008;26(2):169-74. doi: 10.1159/000151050. Epub 2008 Aug 7.

Abstract

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.

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / epidemiology
  • Humans
  • Macular Degeneration / epidemiology
  • Macular Degeneration / genetics
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors

Substances

  • ARMS2 protein, human
  • Apolipoprotein E4
  • Proteins