title: Genetic variation in the choline acetyltransferase (CHAT) gene may be associated with the risk of Alzheimer's disease.
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.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, 624 Parran Hall, Pittsburgh, PA 15261, USA.
authors.forename: Ayla
authors.initials: A
authors.lastname: Ozturk
authors.forename: Steven T
authors.initials: ST
authors.lastname: DeKosky
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D010414:Pennsylvania / Q000453:epidemiology; D011110:Polymorphism, Genetic; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D002795:Choline O-Acetyltransferase