Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 19, Issue 1, Pages 171-177Publisher
IOS PRESS
DOI: 10.3233/JAD-2010-1225
Keywords
Frontotemporal Lobar Degeneration (FTLD); polymorphism; progranulin (GRN); risk factor; variability
Categories
Funding
- Associazione Amici del Centro Dino Ferrari
- Monzino Foundation
- IRCCS Ospedale Maggiore Milano
- Associazione per la Ricerca sulle Demenze (ARD)
- Ricerca Corrente
- Italian Ministry of Health
- Ing. Cesare Cusan
- [PS-NEURO ex 56/05/4]
- [PS-NEURO ex 56/05/11]
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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 to 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.
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