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.
2008 Wiley-Liss, Inc.