No association between familial Alzheimer disease and cytochrome P450 polymorphisms

Four different loci have been found to be involved in the development of familial Alzheimer disease (AD). The epsilon 4 allele of the apolipoprotein E gene on chromosome 19 is a susceptibility factor for AD, and in a small number of AD families, dominant mutations with high penetrance are operating in genes on chromosomes 1, 14 and 21. However, the disease in many familial AD cases cannot be explained by these genes; thus, other genetic factors involved in the etiology of AD should exist. Recently, an association between the cytochrome P450 2D6B (CYP2D6B) allele and the Lewy body variant of AD was reported. In the present study, 54 unrelated Swedish familial AD patients and 56 age- and sex-matched healthy controls were studied with respect to the two genetic polymorphisms of oxidative drug metabolism, CYP2D6 and CYP2C19. No significant association was found between the defect CYP2D6A and -B or CYP2C19m1 and -m2 alleles and familial AD patients, with the exception of a lower frequency of CYP2D6B in the male AD cases.