Viswanathan Jayashree, Mäkinen Petra, Helisalmi Seppo, Haapasalo Annakaisa, Soininen Hilkka, Hiltunen Mikko
Department of Neurology, Clinical Research Centre/Mediteknia, University Hospital and University of Kuopio, Finland.
Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 5;150B(5):747-50. doi: 10.1002/ajmg.b.30889.
Granulin protein plays an important role in neurite outgrowth and neuronal survival. Recently, it was shown that mutations in granulin (GRN) gene cause tau-negative frontotemporal dementia supporting the idea that granulin is involved in neurodegeneration. Here we have investigated whether genetic variability in the GRN gene influences also the risk of developing Alzheimer's disease (AD). Genotyping of six single nucleotide polymorphisms (SNPs) in the GRN gene among 512 AD patients and 649 control subjects originating from Finland did not show significant association with AD. However, stratification according to gender revealed a significant male-specific allele, genotype and haplotype association between AD and GRN SNPs rs4792939, rs850713, and rs5848. These data suggest that genetic variability in the GRN gene may also increase the risk for developing AD in a gender-specific manner.
颗粒蛋白在神经突生长和神经元存活中发挥着重要作用。最近的研究表明,颗粒蛋白(GRN)基因突变会导致tau蛋白阴性额颞叶痴呆,这支持了颗粒蛋白参与神经退行性变的观点。在此,我们研究了GRN基因的遗传变异性是否也会影响患阿尔茨海默病(AD)的风险。对来自芬兰的512名AD患者和649名对照受试者的GRN基因中的六个单核苷酸多态性(SNP)进行基因分型,结果显示与AD无显著关联。然而,按性别分层后发现,AD与GRN基因SNP rs4792939、rs850713和rs5848之间存在显著的男性特异性等位基因、基因型和单倍型关联。这些数据表明,GRN基因的遗传变异性也可能以性别特异性方式增加患AD的风险。