ApoE-ε 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 ( r 2 = 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-e4 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. Conclusion There is considerable effect of the ChAT polymorphisms on AD in Korean population and this effect is dependent on ApoE genotypes.