TY - JOUR
T1 - Rs5848 polymorphism and serum progranulin level
AU - Hsiung, Ging Yuek R.
AU - Fok, Alice
AU - Feldman, Howard H.
AU - Rademakers, Rosa
AU - MacKenzie, Ian R.A.
N1 - Funding Information:
This study is supported by grants from the Canadian Institute of Health Research (CIHR) # 74580 and # 179009 , the Pacific Alzheimer Research Foundation # C06-01 (to IRAM & HHF), and the NIH R01 NS 065782 (RR), as well as donations to the UBC Clinic for Alzheimer and Related Disorders from the Townsend Family. Dr. Hsiung is supported by a Clinical Genetics Investigatorship award from the CIHR. We would like to thank Pheth Sengdy for coordinating and arranging clinical assessment for all at-risk FTD subjects enrolled in this project. We are also indebted to all the patients and families who donated their time and effort in their participation of this research.
PY - 2011/1/15
Y1 - 2011/1/15
N2 - 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.
AB - 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.
KW - Biomarker
KW - Frontotemporal dementia
KW - GRN
KW - Genetic polymorphism
KW - PGRN
KW - Progranulin
KW - Rs5848
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U2 - 10.1016/j.jns.2010.10.009
DO - 10.1016/j.jns.2010.10.009
M3 - Article
C2 - 21047645
AN - SCOPUS:78650511054
SN - 0022-510X
VL - 300
SP - 28
EP - 32
JO - Journal of the neurological sciences
JF - Journal of the neurological sciences
IS - 1-2
ER -