Corbo Rosa Maria, Gambina Giuseppe, Ulizzi Laura, Moretto Giuseppe, Scacchi Renato
Department of Genetics and Molecular Biology, University La Sapienza, IT-00185 Rome, Italy.
Dement Geriatr Cogn Disord. 2009;27(6):513-8. doi: 10.1159/000221832. Epub 2009 May 29.
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 gender-specific 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.
We analyzed the role of 3 CYP19 single-nucleotide 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.
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.
Together with gender-specific factors such as parity, genes controlling estrogen metabolism may play a relevant role in AD susceptibility in women.
背景/目的：有证据表明女性患阿尔茨海默病（AD）的患病率较高，但这是由于她们较长的预期寿命还是生物学上的性别特异性风险因素尚不清楚。一个可能的促成因素是绝经后雌激素神经保护作用的降低。在这种情况下，一个AD风险基因可能是CYP19，它编码芳香化酶，一种参与雌激素生物合成的酶。
我们分析了3个CYP19单核苷酸多态性（rs12907866、rs17601241、rs4646）在AD发病中的作用，以及它们对319例患者和110例对照中反映疾病严重程度的定量性状（发病年龄和认知衰退）的可能影响。
未观察到CYP19单核苷酸多态性与AD风险之间的关联。然而，CYP19基因变异似乎确实在女性AD发病中起作用，因为携带T等位基因的rs4646基因型与较早的发病年龄相关（p = 0.01），独立于由APOE ε4等位基因确定的类似效应（p = 0.005）。此外，rs4646基因型对发病年龄的影响似乎仅在有生育史的女性中存在（p = 0.01），且似乎取决于过去的生育情况。
与生育情况等性别特异性因素一起，控制雌激素代谢的基因可能在女性AD易感性中起相关作用。
