科学家们发现，女性在X染色体上的一种基因变异与阿尔茨海默氏症风险的增加有关，新成果发表在2009年1月11日在线出版的《自然—遗传学》（Nature Genetics） 期刊上。这是在阿尔茨海默氏症疾病的研究中首次发现的与性别相关的基因风险因子证据。
晚发性阿尔茨海默氏症是一种神经退化性疾病，也是引发老年痴呆症的主要诱因。基因APOE上的变异是已知的重复出现的遗传风险因子。美国梅奥诊所医学院的Steven Younkin和同事对阿尔茨海默氏症患者实施了泛基因组相关性研究。他们发现，在统计学上，在PCDH11X基因中鉴别出的一种变异与这种疾病的易感性高度相关。在分析这些数据与性别的关系时，他们发现这种相关性几乎只局限于女性。PCDH11X负责编码一种名为原钙黏蛋白的蛋白质，这种蛋白质是促进分子间粘连的分子家族中的一员，是中枢神经系统的信号分子。
部分证据显示，一种与早发性阿尔茨海默氏症相关的酶会将原钙蛋白分裂成活跃形式。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Genetics，doi:10.1038/ng.305，Minerva M Carrasquillo，Steven G Younkin
Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease
Minerva M Carrasquillo1, Fanggeng Zou1, V Shane Pankratz2, Samantha L Wilcox1, Li Ma1, Louise P Walker1, Samuel G Younkin1, Curtis S Younkin1, Linda H Younkin1, Gina D Bisceglio1, Nilufer Ertekin-Taner1,3, Julia E Crook4, Dennis W Dickson1, Ronald C Petersen3,5, Neill R Graff-Radford1,3 & Steven G Younkin1
By analyzing late-onset Alzheimer's disease (LOAD) in a genome-wide association study (313,504 SNPs, three series, 844 cases and 1,255 controls) and evaluating the 25 SNPs with the most significant allelic association in four additional series (1,547 cases and 1,209 controls), we identified a SNP (rs5984894) on Xq21.3 in PCDH11X that is strongly associated with LOAD in individuals of European descent from the United States. Analysis of rs5984894 by multivariable logistic regression adjusted for sex gave global P values of 5.7 × 10-5 in stage 1, 4.8 × 10-6 in stage 2 and 3.9 × 10-12 in the combined data. Odds ratios were 1.75 (95% CI = 1.42–2.16) for female homozygotes (P = 2.0 × 10-7) and 1.26 (95% CI = 1.05–1.51) for female heterozygotes (P = 0.01) compared to female noncarriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99–1.41).
1 Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
2 Division of Biomedical Statistics and Informatics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
3 Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
4 Biostatistics Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
5 Mayo Alzheimer Disease Research Center, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
