Butyrylcholinesterase K variant is genetically associated with late onset Alzheimer's disease in Northern Ireland

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that h as been associated, sometimes controversially, with polymorphisms in a numb er of genes. Recently the butyrylcholinesterase K variant (BCHE K) allele h as been shown to act in synergy with the apolipoprotein E epsilon 4 (APOE e psilon 4) allele to promote risk for AD. Most subsequent replicative studie s have been unable to confirm these findings. We have conducted a case-cont rol association study using a clinically well defined group of late onset A D patients (n=175) and age and sex matched control subjects (n=187) from th e relatively genetically homogeneous Northern Ireland population to test th is association. The BCHE genotypes of patients were found to be significant ly different from controls (chi(2)=23.68, df=2, p much less than 0.001). Th e frequency of the K variant allele was also found to differ significantly in cases compared to controls (chi(2)=16.39, df=1, p much less than 0.001) leading to an increased risk of AD in subjects with this allele (OR=3.50, 9 5% CI 2.20-6.07). This risk increased in subjects 75 years and older (OR=5. 50, 95% CI 2.56-11.87). At the same time the APOE epsilon 4 associated risk was found to decrease from 6.70 (95% CI 2.40-19.04) in 65-74 year olds to 3.05 (95% CI 1.34-6.95) in those subjects 75 years and older. However, we d etected no evidence of synergy between BCHE K and APOE epsilon 4. The resul ts from this study suggest that possession of the BCHE K allele constitutes a significant risk for AD in the Northern ireland population and, furtherm ore, this risk increases with increasing age.