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

Ozturk, Ayla; DeKosky, Steven T.; Kamboh, M. Ilyas

doi:10.1016/j.neurobiolaging.2005.08.024

« Previous Next »Neurobiology of Aging
Volume 27, Issue 10 , Pages 1440-1444, October 2006

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

Ayla Ozturk
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, 624 Parran Hall, Pittsburgh, PA 15261, USA
Steven T. DeKosky
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, 624 Parran Hall, Pittsburgh, PA 15261, USA
- Alzheimer's Disease Research Center, School of Medicine, University of Pittsburgh, PA 15213, USA
- Department of Neurology, School of Medicine, University of Pittsburgh, PA 15213, USA
M. Ilyas Kamboh
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, 624 Parran Hall, Pittsburgh, PA 15261, USA
- Alzheimer's Disease Research Center, School of Medicine, University of Pittsburgh, PA 15213, USA
- Corresponding author. Tel.: +1 412 624 3066; fax: +1 412 383 7844.

Received 17 May 2005; received in revised form 27 July 2005; accepted 20 August 2005. published online 13 October 2005.

Abstract

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.