ApoE-epsilon 4-dependent association of the choline acetyltransferase gene polymorphisms (2384G>A and 1882G>A) with Alzheimer's disease.
BACKGROUND
One of the characteristic features of Alzheimer's disease (AD) is the degeneration of the cholinergic system. The gene encoding choline acetyltransferase (ChAT), a key enzyme in cholinergic function, is a candidate gene conferring risk for AD. But the genetic association of the enzyme with AD has been controversial. We analyzed 2 ChAT single nucleotide polymorphisms (SNPs), 2384G>A (rs3810950; Ala120Thr) and 1882G>A (rs1880676; Asp7Asn) and the ApoE polymorphisms in Korean population.


METHODS
The samples from 316 AD patients and 264 age-matched healthy controls were analyzed. The differences in genotype frequencies were assessed.


RESULTS
The 2 ChAT SNPs were almost completely linked with each other (r2=0.99, |D'|=1.0). No significant difference in the ChAT genotype distribution was observed between the patients and the controls. However, in non-ApoE-epsilon4 allele carriers, multiple logistic regression analysis showed that both the GA and the GA/AA genotypes were associated with AD (OR=1.639, 95% CI, 1.050-2.559, p=0.0297 for GA; OR=1.630, 95% CI, 1.049-2.532, p=0.0297 for GA/AA), suggesting a dominant effect of A allele.


CONCLUSIONS
There is considerable effect of the ChAT polymorphisms on AD in Korean population and this effect is dependent on ApoE genotypes.
Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul, South Korea. sangmeeaj@nih.go.kr
Sangmee
S
Ahn Jo
Kyungsook
K
Ahn
Ji-Hyun
JH
Kim
Byung-Hak
BH
Kang
Eunkyung
E
Kim
Inho
I
Jo
Doh Kwan
DK
Kim
D000241:Adenosine / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006151:Guanosine / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D006151:Guanosine; D002795:Choline O-Acetyltransferase; D000241:Adenosine