Interaction between CYP19 aromatase and butyrylcholinesterase genes increases Alzheimer's disease risk

Biological evidence supports a role of aromatase and butyrilcholinesterase ( BCHE) enzymes in the disruption of the cholinergic neurotransmission observed in Alzheimer's disease ( AD). Estrogens may reduce the risk of AD through enhancing or preserving cholinergic neurotransmission, and aromatase, the product of the CYP19 gene, is a critical enzyme in the peripheral synthesis of estrogens. BCHE is a hydrolytic enzyme associated with acetylcholine synaptic degradation, and the BCHE K genetic variant confers some protective effect for AD by reducing the activity of the enzyme. We investigated whether a 5'-UTR CYP19 polymorphism and the BCHE K variant might be responsible for susceptibility to AD by studying a clinically well-defined group of 187 sporadic AD patients and 172 control subjects from a Spanish population. We have shown that the CYP19 C/C genotype is overrepresented in AD patients who carry the BCHE non-K allele when compared with controls ( OR = 1.85, p = 0.03). Our findings suggest that the CYP19 and BCHE polymorphisms may interact in determining the risk of AD. Copyright (C) 2005 S. Karger AG, Basel.