科學(xué)家們發(fā)現(xiàn),，女性在X染色體上的一種基因變異與阿爾茨海默氏癥風(fēng)險(xiǎn)的增加有關(guān),，新成果發(fā)表在2009年1月11日在線出版的《自然—遺傳學(xué)》（Nature Genetics） 期刊上,。這是在阿爾茨海默氏癥疾病的研究中首次發(fā)現(xiàn)的與性別相關(guān)的基因風(fēng)險(xiǎn)因子證據(jù),。
晚發(fā)性阿爾茨海默氏癥是一種神經(jīng)退化性疾病,，也是引發(fā)老年癡呆癥的主要誘因,。基因APOE上的變異是已知的重復(fù)出現(xiàn)的遺傳風(fēng)險(xiǎn)因子,。美國梅奧診所醫(yī)學(xué)院的Steven Younkin和同事對(duì)阿爾茨海默氏癥患者實(shí)施了泛基因組相關(guān)性研究。他們發(fā)現(xiàn),，在統(tǒng)計(jì)學(xué)上,，在PCDH11X基因中鑒別出的一種變異與這種疾病的易感性高度相關(guān)。在分析這些數(shù)據(jù)與性別的關(guān)系時(shí),，他們發(fā)現(xiàn)這種相關(guān)性幾乎只局限于女性,。PCDH11X負(fù)責(zé)編碼一種名為原鈣黏蛋白的蛋白質(zhì)，這種蛋白質(zhì)是促進(jìn)分子間粘連的分子家族中的一員,，是中樞神經(jīng)系統(tǒng)的信號(hào)分子,。
部分證據(jù)顯示，一種與早發(fā)性阿爾茨海默氏癥相關(guān)的酶會(huì)將原鈣蛋白分裂成活躍形式,。（生物谷Bioon.com）
生物谷推薦原始出處：
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
