Bettens Karolien, Brouwers Nathalie, Engelborghs Sebastiaan, De Deyn Peter P, Van Broeckhoven Christine, Sleegers Kristel
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Antwerpen, Belgium.
Hum Mutat. 2008 May;29(5):769-70. doi: 10.1002/humu.20725.
SORL1 has recently been identified as a major genetic contributor to increased risk for late-onset Alzheimer disease (AD). Here we aimed at replicating this finding in a large, well-characterized group of 550 Belgian late-onset AD patients and 637 healthy control individuals using a gene-wide genotyping approach across the SORL1 locus. We observed significant associations, both for individual SNPs (SNPs 6, 8, 9, 10 and 27; p-values ranging from 0.001 to 0.040) and 3-SNP haplotypes (SNPs 5-6-7 and SNPs 25-26-27; p-values ranging from 0.008 to 0.035). Moreover, the associations at SNP 8, 9 and 10 represented a direct replication of the initial association data. Two signals in distinct regions of the gene were shown to be mutually independent, supporting allelic heterogeneity at the SORL1 locus in the Belgian population. Our findings confirm that genetic variants in SORL1 may be important risk factors for late-onset AD.
SORL1最近被确定为晚发性阿尔茨海默病(AD)风险增加的主要遗传因素。在此,我们旨在通过对SORL1基因座进行全基因分型,在550名比利时晚发性AD患者和637名健康对照个体组成的大型、特征明确的群体中重复这一发现。我们观察到,无论是单个单核苷酸多态性(SNP,即SNP 6、8、9、10和27;P值范围为0.001至0.040)还是3-SNP单倍型(SNP 5-6-7和SNP 25-26-27;P值范围为0.008至0.035),都存在显著关联。此外,SNP 8、9和10处的关联直接重复了最初的关联数据。该基因不同区域的两个信号相互独立,这支持了比利时人群中SORL1基因座的等位基因异质性。我们的研究结果证实,SORL1中的遗传变异可能是晚发性AD的重要风险因素。