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. © 2010 - IOS Press and the authors. All rights reserved.

Galimberti, D., Fenoglio, C., Cortini, F., Serpente, M., Venturelli, E., Villa, C., et al. (2010). GRN variability contributes to sporadic frontotemporal lobar degeneration. JOURNAL OF ALZHEIMER'S DISEASE, 19(1), 171-177 [10.3233/JAD-2010-1225].

GRN variability contributes to sporadic frontotemporal lobar degeneration

Villa C.;
2010

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. © 2010 - IOS Press and the authors. All rights reserved.
Articolo in rivista - Articolo scientifico
Frontotemporal Lobar Degeneration (FTLD)
Polymorphism
Progranulin (GRN)
Risk factor
Variability
Aged
Female
Frontotemporal Lobar Degeneration
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Intercellular Signaling Peptides and Proteins
Male
Middle Aged
Polymorphism, Single Nucleotide
Progranulins
Protein Precursors
Risk Factors
English
171
177
7
Galimberti, D., Fenoglio, C., Cortini, F., Serpente, M., Venturelli, E., Villa, C., et al. (2010). GRN variability contributes to sporadic frontotemporal lobar degeneration. JOURNAL OF ALZHEIMER'S DISEASE, 19(1), 171-177 [10.3233/JAD-2010-1225].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/281894
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