ParkinsonCanadaV1, Main, Exploration, bibRecord, 001972

rs5848 Polymorphism and Serum Progranulin Level

Identifieur interne : 001972 ( Main/Exploration ); précédent : 001971; suivant : 001973

rs5848 Polymorphism and Serum Progranulin Level

Auteurs : Ging-Yuek R. Hsiung [Canada] ; Alice Fok [Canada] ; Howard H. Feldman [Canada, États-Unis] ; Rosa Rademakers [États-Unis] ; Ian R. A. Mackenzie [Canada]

Source :

Journal of the neurological sciences [ 0022-510X ] ; 2010.

RBID : PMC:3085023

Abstract

Objective

To assess the influence of rs5848 polymorphism in serum progranulin (PGRN) level in a cohort of subjects with Alzheimer and related dementias from a tertiary referral clinic.

Background

Mutations in the GRN gene cause autosomal dominant frontotemporal dementia (FTD) with TDP-43 pathology (FTLD-TDP) through haploinsufficiency. It has recently been shown that homozygous carriers of the T-allele of rs5848 have an elevated risk developing FTD, and this polymorphism may play a role in the pathogenesis of other dementia by modifying progranulin level. We hypothesize that genotype of rs5848 may influence serum PGRN level in AD, FTD, and other dementias.

Methods

Blood samples were obtained from patients with cognitive impairment and dementia referred to a tertiary dementia clinic, as well as samples from a cohort of healthy controls. Serum PGRN level was measured using an ELISA assay, and rs5848 genotype was determined by a TaqMan assay.

Results

We found that rs5848 SNP significantly influenced serum PGRN level, with TT genotype having the lowest levels, CC the highest. This relationship is observed in each of the subgroups. We also confirmed that GRN mutation carriers had significantly lower serum PGRN levels than all other groups.

Conclusions

The rs5848 polymorphism significantly influences serum PGRN with TT carriers having a lower level of serum PGRN then CT and CC carriers. This is consistent with the finding that miR-659 binding to the high risk T allele of rs5848 may augment translational inhibition of GRN and alter risk of FTD and possibly other dementias.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085023

DOI: 10.1016/j.jns.2010.10.009
PubMed: 21047645
PubMed Central: 3085023

Affiliations:

Canada, États-Unis

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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objective</title>
<p id="P1">To assess the influence of rs5848 polymorphism in serum progranulin (PGRN) level in a cohort of subjects with Alzheimer and related dementias from a tertiary referral clinic.</p>
</sec>
<sec id="S2"><title>Background</title>
<p id="P2">Mutations in the <italic>GRN</italic>
 gene cause autosomal dominant frontotemporal dementia (FTD) with TDP-43 pathology (FTLD-TDP) through haploinsufficiency. It has recently been shown that homozygous carriers of the T-allele of rs5848 have an elevated risk developing FTD, and this polymorphism may play a role in the pathogenesis of other dementia by modifying progranulin level. We hypothesize that genotype of rs5848 may influence serum PGRN level in AD, FTD, and other dementias.</p>
</sec>
<sec sec-type="methods" id="S3"><title>Methods</title>
<p id="P3">Blood samples were obtained from patients with cognitive impairment and dementia referred to a tertiary dementia clinic, as well as samples from a cohort of healthy controls. Serum PGRN level was measured using an ELISA assay, and rs5848 genotype was determined by a TaqMan assay.</p>
</sec>
<sec id="S4"><title>Results</title>
<p id="P4">We found that rs5848 SNP significantly influenced serum PGRN level, with TT genotype having the lowest levels, CC the highest. This relationship is observed in each of the subgroups. We also confirmed that <italic>GRN</italic>
 mutation carriers had significantly lower serum PGRN levels than all other groups.</p>
</sec>
<sec id="S5"><title>Conclusions</title>
<p id="P5">The rs5848 polymorphism significantly influences serum PGRN with TT carriers having a lower level of serum PGRN then CT and CC carriers. This is consistent with the finding that miR-659 binding to the high risk T allele of rs5848 may augment translational inhibition of <italic>GRN</italic>
 and alter risk of FTD and possibly other dementias.</p>
</sec>
</div>
</front>
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La maladie de Parkinson au Canada (serveur d'exploration)

rs5848 Polymorphism and Serum Progranulin Level

rs5848 Polymorphism and Serum Progranulin Level

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