Huang R, Poduslo S E
J Med Genet. 2006 Aug;43(8):e42. doi: 10.1136/jmg.2005.039461.
Cytochrome P450 aromatase, an enzyme that catalyses the conversion of androgens to oestrogen, is expressed at high levels in the gonads and in the brain. Aromatase activity is increased in the nucleus basalis of Meynert during aging and in Alzheimer's disease (AD), making the gene (CYP19), at 15q21.1, a potential candidate risk factor. We examined 18 single nucleotide polymorphisms spanning the 5'-untranslated region and the entire coding region of CYP19 in 227 patients with AD and 131 control spouses. We found that the gene region could be divided into two haplotype blocks; a haplotype in block 1 and a haplotype in block 2 increased the risk of developing the disease by twofold in APOE 4 carriers. The implication of two haplotypes conferring increased risk for AD warrants further investigation of the regulation of aromatase activity in brain.
细胞色素P450芳香化酶是一种催化雄激素转化为雌激素的酶，在性腺和大脑中高水平表达。在衰老过程和阿尔茨海默病（AD）中，Meynert基底核中的芳香化酶活性增加，使得位于15q21.1的基因（CYP19）成为一个潜在的候选风险因素。我们检测了227例AD患者和131例对照配偶中跨越CYP19基因5'-非翻译区和整个编码区的18个单核苷酸多态性。我们发现该基因区域可分为两个单倍型块；在APOE 4携带者中，第1块中的一个单倍型和第2块中的一个单倍型使患该病的风险增加了两倍。两种单倍型增加AD风险这一情况，需要对大脑中芳香化酶活性的调节进行进一步研究。
