Assareh Amelia A, Piguet Olivier, Lye Tanya C, Mather Karen A, Broe Gerald A, Schofield Peter R, Sachdev Perminder S, Kwok John B J
Neuroscience Research Australia, Sydney, Australia.
Curr Alzheimer Res. 2014;11(6):558-63. doi: 10.2174/1567205011666140618101408.
Sortilin-related receptor, Sorl1, is a neuronal receptor that interacts with the amyloid precursor protein to regulate amyloidogenesis. Variants in the gene encoding Sorl1 are associated with Alzheimer's disease (AD), as well as its neuroimaging markers.
To investigate the relationship between SORL1 gene variants with ADrelated brain morphologies and AD, testing for sex-specific effects.
The sample comprised 292 individuals aged ≥ 75 years participating in the longitudinal Sydney Older Persons Study. A sub-sample also underwent a brain MRI scan (n=102, 53 males; 49 females). The relationships of three SORL1 single nucleotide polymorphisms (SNPs): rs4935774, rs2298813, rs1133174 with brain MRI measures, and AD were determined.
Significant associations of SORL1 variants with cross-sectional brain MRI measures and AD were observed only when the sample was stratified by sex. The most common haplotype (H1), comprising rs4935774-T, rs2298813-G, and rs1133174-G alleles (T/G/G) was associated with whole brain atrophy in both males and females (p=0.012 & p=0.013; respectively). Only SNP rs1133174 was individually associated with hippocampal atrophy in males (p= 0.039) and females (p=0.025). Of the 292 participants, 111 had either probable or possible AD. A significant association of H1 with AD (p = 0.017) was observed in females. A nominally significant association of SNP rs1133174 with AD (p = 0.051) was also observed in the whole cohort.
The results provide evidence that the association of polymophisms in the sortilin-related receptor gene (SORL1) with AD and its MRI biomarkers of brain and hippocampal atrophy are moderated by sex.
与sortilin相关的受体Sorl1是一种神经元受体，可与淀粉样前体蛋白相互作用以调节淀粉样蛋白生成。编码Sorl1的基因变异与阿尔茨海默病（AD）及其神经影像学标志物相关。
研究SORL1基因变异与AD相关脑形态及AD之间的关系，并检测性别特异性效应。
样本包括292名年龄≥75岁的参与者，他们参与了纵向悉尼老年人研究。一个子样本还接受了脑部MRI扫描（n = 102，53名男性；49名女性）。确定了三个SORL1单核苷酸多态性（SNP）：rs4935774、rs2298813、rs1133174与脑部MRI测量值及AD之间的关系。
仅当样本按性别分层时，才观察到SORL1变异与横断面脑部MRI测量值及AD之间存在显著关联。最常见的单倍型（H1），由rs4935774-T、rs2298813-G和rs1133174-G等位基因（T/G/G）组成，与男性和女性的全脑萎缩均相关（分别为p = 0.012和p = 0.013）。仅SNP rs1133174分别与男性（p = 0.039）和女性（p = 0.025）的海马萎缩单独相关。在292名参与者中，111人患有可能或疑似AD。在女性中观察到H1与AD存在显著关联（p = 0.017）。在整个队列中也观察到SNP rs1133174与AD存在名义上的显著关联（p = 0.051）。
结果提供了证据表明，sortilin相关受体基因（SORL1）多态性与AD及其脑和海马萎缩的MRI生物标志物之间的关联受性别影响。
