Genetic variation of CYP19 (aromatase) gene influences age at onset of Alzheimer's disease in women.

Background/Aims: There is evidence for a higher prevalence of Alzheimer's disease (AD) in women, but whether this is due to their longer life expectancy or to biological genderspecific risk factors is unclear. One likely contributing factor is the reduced estrogen neuroprotective action following menopause. In this context, an AD risk gene could be CYP19, encoding aromatase, an enzyme involved in estrogen biosynthesis. Methods: We analyzed the role of 3 CYP19 singlenucleotide polymorphisms (rs12907866, rs17601241, rs4646) in AD development and their possible influence on quantitative traits reflecting disease severity (age at onset and cognitive decline) in 319 patients and 110 controls. Results: No association was observed between the CYP19 single-nucleotide polymorphisms and AD risk. Yet CYP19 genetic variation did seem to contribute to AD development in women as the rs4646 genotypes carrying the T allele were associated with an earlier onset age (p = 0.01) independently of a similar effect determined by the APOE e * 4 allele (p = 0.005). Also, being present only in parous women (p = 0.01), the effect of rs4646 genotypes on onset age appeared to depend on past fertility. Conclusion: Together with gender-specific factors such as parity, genes controlling estrogen metabolism may play a relevant role in AD susceptibility in women.