Rs5848 polymorphism and serum progranulin level

Ging Yuek R. Hsiung, Alice Fok, Howard H. Feldman, Rosa Rademakers, Ian R.A. MacKenzie

Research output: Contribution to journalArticle

51 Scopus citations

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 of 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, and CC as 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.

Original languageEnglish (US)
Pages (from-to)28-32
Number of pages5
JournalJournal of the neurological sciences
Volume300
Issue number1-2
DOIs
StatePublished - Jan 15 2011

Keywords

  • Biomarker
  • Frontotemporal dementia
  • GRN
  • Genetic polymorphism
  • PGRN
  • Progranulin
  • Rs5848

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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  • Cite this

    Hsiung, G. Y. R., Fok, A., Feldman, H. H., Rademakers, R., & MacKenzie, I. R. A. (2011). Rs5848 polymorphism and serum progranulin level. Journal of the neurological sciences, 300(1-2), 28-32. https://doi.org/10.1016/j.jns.2010.10.009