Genetic variation in the choline acetyltransferase (CHAT) gene may be associated with the risk of Alzheimer's disease

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Ozturk A., DeKosky S. T., Kamboh M. I.

NEUROBIOLOGY OF AGING, cilt.27, sa.10, ss.1440-1444, 2006 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 10
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1016/j.neurobiolaging.2005.08.024
  • Dergi Adı: NEUROBIOLOGY OF AGING
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1440-1444
  • Anahtar Kelimeler: Alzheimer's disease, genetics, CHAT, age-at-onset, MMSE, SINGLE NUCLEOTIDE POLYMORPHISM, APOLIPOPROTEIN-E EPSILON-4, ONSET, LINKAGE, DEMENTIA, LOCUS
  • Erciyes Üniversitesi Adresli: Hayır

Özet

Several independent linkage studies have mapped a broad susceptibility region for Alzheimer's disease (AD) on the long arm of chromosome 10. There are several biological candidate genes in this region, including choline acetyltransferase (CHAT). A number of studies have examined the role of CHAT genetic variants with AD risk and age-at-onset (AAO), but the results are equivocal. We examined the association of three Single Nucleotide Polymorphisms (SNPs) in the CHAT gene in 1001 white sporadic late-onset AD (LOAD) cases and 708 white controls. We also examined the role of these three SNP with quantitative traits of AD including AAO, disease duration, and Mini-Mental State Examination (MMSE) score. We observed both allelic and genotypic associations of the intron 9 SNP with AD risk in the total sample (P=0.029 for genotype and p = 0.028 for allele frequency differences) as well as among non-APOE*4 carriers (p = 0.007 for genotype and p = 0.006 for allele frequency differences). Three-site haplotype analysis confirmed that haplotypes determined by the intron 9 SNP were associated with either risk (p = 0.0009) or protective (p = 0.0082) effects among non-APOE*4 carriers. The three CHAT SNPs also showed a modest association with MMSE score. Our data suggest that genetic variation in the CHAT gene may be associated with AD risk and quantitative traits related to AD. (c) 2005 Elsevier Inc. All rights reserved.