Objective: To perform an association study of rs9897526 and rs5848 in the gene encoding for Progranulin (PGRN) in Multiple Sclerosis (MS) patients with and without cognitive impairment as compared with age-matched controls to determine whether the presence of these variants influences the susceptibility to MS or to the development of cognitive impairment during the course of the disease. Background: PGRN is 593 aminoacid secreted glycoprotein which is expressed in many tissues, including the Central Nervous System.Mutations in PGRN are responsible for familial Frontotemporal Lobar Degeneration with ubiquitin pathology. Progranulin is highly expressed in microglial cells and likely plays a role in neurodegeneration.To date, studies about the role of this protein in cognitive decline occurring in MS patients are still lacking. Methods: Preliminary case-control study was performed in 154 patients with MS (of which 19 with cognitive impairment, evaluated through neuropsychological testing) and 144 controls for rs9897526 and rs5848 Single Nucleotide Polymorphisms (SNPs) by allelic discrimination using an ABI PRISM 7000 instrument (ABI). Haploview software was used to test for association. Results: No significant differences were found between patients, either with cognitive decline or not, and controls. However, a tendency towards an increase of the frequency of rs5848 T/T genotype was found in MS patients compared with controls (16% versus 7%, P>0.05).No differences were found stratifying according to gender or the subtype of MS. Conclusion: PGRN likely doesn¡ıt influence either the susceptibility to develop MS, or the risk to have cognitive impairment during the course of the disease.However, these results need to be confirmed in a wider population to draw definitive conclusions.
|Titolo:||Progranulin gene mutation scanning in multiple sclerosis patients with cognitive impairment|
|Data di pubblicazione:||giu-2008|
|Digital Object Identifier (DOI):||10.1007/s00415-007-0711-8|
|Appare nelle tipologie:||01 - Articolo su periodico|