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- Title
GRN Variability Contributes to Sporadic Frontotemporal Lobar Degeneration.
- Authors
Galimberti, Daniela; Fenoglio, Chiara; Cortini, Francesca; Serpente, Maria; Venturelli, Eliana; Villa, Chiara; Clerici, Francesca; Marcone, Alessandra; Benussi, Luisa; Ghidoni, Roberta; Gallone, Salvatore; Scalabrini, Diego; Restelli, Ilaria; Boneschi, Filippo Martinelli; Cappa, Stefano; Binetti, Giuliano; Mariani, Claudio; Rainero, Innocenzo; Giordana, Maria Teresa; Bresolin, Nereo
- Abstract
Mutations in the 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 a GRN causal mutation, and 375 age-matched controls. Four tagging Single Nucleotide Polymorphisms (SNPs) were chosen generate 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. Our findings indicate that the 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 may be of mechanistic importance.
- Subjects
GENETIC mutation; GENES; UBIQUITIN; NUCLEOTIDES; CHROMOSOME polymorphism; BRAIN degeneration
- Publication
Journal of Alzheimer's Disease, 2010, Vol 19, Issue 1, p171
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2010-1225