Consistent deficits in the cholinergic system are evident in the brains of Alzheimer's Disease (AD) patients, including reductions in the activities of acetylcholine, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT), increased butyrylcholinesterase (BChE) activity, and a selective loss of nicotinic acetylcholine receptors (nAChRs). Accordingly, we have analyzed polymorphisms in the genes encoding AChE, ChAT, BChE, and several of the subunit genes from neuronal nAChRs, for genetic associations with late-onset AD. A significant association for disease was detected for a non-coding polymorphism in ChAT (allele χ1 2 = 12.84, P = 0.0003; genotype χ2 2 = 11.89, P = 0.0026). Although replication analysis did not confirm the significance of this finding when the replication samples were considered alone (allele χ1 2 = 1.02, P=0.32; genotype χ2 2 = 1.101, P = 0.58) the trends were in the correct direction and a significant association remained when the two sample sets were pooled (allele χ1 2 = 12.37, P = 0.0004; genotype χ2 2 = 11.61, P = 0.003). Previous studies have reported significant disease associations for both the K-variant of BChE and the coding ChAT rs3810950 polymorphism with AD. Replication analyses of these two loci failed to detect any significant association for disease in our case-control samples.
|Number of pages||4|
|Journal||American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics|
|Early online date||22 Dec 2004|
|Publication status||Published - 5 Jan 2005|