Mutations in progranulin gene (GRN) are responsible for familial FTLD with ubiquitin pathology (FTLD-U). However, there are controversial data regarding the contribution of GRN variability to sporadic FTLD. We carried out an association study in 265 patients who did not carry any GRN causal mutation compared with 375 age-matched controls. To this aim, four tagging Single Nucleotide Polymorphisms (SNPs) were chosen in order to get 80\% power to detect an allelic association with P 0.01. In addition, a known functional SNP (rs5848) was included. An increased frequency of the rs4792938 CC genotype in cases compared with controls was observed (17.4 versus 10.4\%, P=0.01, OR: 1.81, 95\%CI: 1.15-2.85). Stratifying for gender, no differences were observed for all polymorphisms. Haplotype analysis failed to detect haplotypes associated with the disease. GRN rs4792938 CC genotype represents a susceptibility factor for the development of FTLD in individuals who do not carry GRN causal mutations. This SNP is likely located in a regulatory region, thus an effect on GRN mRNA levels could be conceivable.