Chapuis Julien, Hannequin Didier, Pasquier Florence, Bentham Peter, Brice Alexis, Leber Isabelle, Frebourg Thierry, Deleuze Jean-François, Cousin Emmanuelle, Thaker Uma, Amouyel Philippe, Mann David, Lendon Corinne, Campion Dominique, Lambert Jean-Charles
INSERM,U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France.
Neurobiol Dis. 2008 Apr;30(1):103-6. doi: 10.1016/j.nbd.2007.12.006. Epub 2008 Jan 5.
The first genome-wide association in Alzheimer's disease (AD) suggested that the GAB2 gene rs2373115 polymorphism may be a strong risk factor in APOE varepsilon4-carriers. We failed to detect an association of rs2373115 with the risk of developing AD in three populations (totalling 1406 controls and 1749 AD cases) whatever the APOE status, even if we observed a slight tendency for an increase of the GG genotype (OR (GG versus GT+TT)=1.3, 95% CI 1.0-1.6, p=0.09) and the G allele frequency (OR=1.3, 95%CI 1.0-1.6, p=0.05) in varepsilon4-carriers. In addition, the rs2373115 did not modulate the extent of tau phosphorylation in the brain of 89 AD cases. The GAB2 gene is at best a minor genetic determinant of AD.
阿尔茨海默病（AD）的首个全基因组关联研究表明，GAB2基因rs2373115多态性可能是APOE ε4携带者患AD的一个重要风险因素。无论APOE状态如何，我们在三个群体（共1406名对照和1749例AD病例）中均未检测到rs2373115与患AD风险之间的关联，即便我们在ε4携带者中观察到GG基因型（OR（GG对GT + TT）= 1.3，95%CI 1.0 - 1.6，p = 0.09）和G等位基因频率（OR = 1.3，95%CI 1.0 - 1.6，p = 0.05）有轻微上升趋势。此外，rs2373115并未调节89例AD病例大脑中tau蛋白的磷酸化程度。GAB2基因充其量只是AD的一个次要遗传决定因素。
