Iivonen S, Corder E, Lehtovirta M, Helisalmi S, Mannermaa A, Vepsäläinen S, Hänninen T, Soininen H, Hiltunen M
Department of Neuroscience and Neurology, University Hospital and University of Kuopio, Finland.
Neurology. 2004 Apr 13;62(7):1170-6. doi: 10.1212/01.wnl.0000118208.16939.60.
Brain aromatase may be neuroprotective by increasing the local estrogen levels in injured neurons. Aromatase is encoded by the CYP19 gene located at 15q21.1, a chromosomal region in linkage disequilibrium (LD) with Alzheimer disease (AD) in this sample.
To investigate whether nine single-nucleotide polymorphisms (SNP) spanning the CYP19 gene were associated with AD.
Three hundred ninety-four patients were compared with 469 nondemented control subjects using single-locus and haplotype approaches. Haplotypes were identified using the expectation/maximization algorithm and latent class analysis, which included additional information on age, sex, and APOE polymorphism.
Allelic and genotypic frequencies for three adjacent SNP differed between AD and control groups. Both haplotype approaches identified an approximately 60% increase (p = 0.02) in the risk of AD for one haplotype and similar levels of excess risk irrespective of APOE polymorphism and gender.
Genetic variation in the brain aromatase gene may modify the risk for AD.
脑芳香化酶可能通过提高受损神经元局部雌激素水平起到神经保护作用。芳香化酶由位于15q21.1的CYP19基因编码，在本样本中该染色体区域与阿尔茨海默病（AD）处于连锁不平衡（LD）状态。
研究跨越CYP19基因的9个单核苷酸多态性（SNP）是否与AD相关。
采用单基因座和单倍型方法，将394例患者与469例非痴呆对照者进行比较。使用期望/最大化算法和潜在类别分析确定单倍型，其中包括年龄、性别和载脂蛋白E（APOE）多态性的附加信息。
AD组和对照组之间三个相邻SNP的等位基因和基因型频率存在差异。两种单倍型方法均显示，一种单倍型使AD风险增加约60%（p = 0.02），且无论APOE多态性和性别如何，风险增加水平相似。
脑芳香化酶基因的遗传变异可能改变AD风险。
