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01-04-2015 | Original Communication

Association of progranulin polymorphism rs5848 with neurodegenerative diseases: a meta-analysis

Authors: Yongdui Chen, Siqi Li, Liling Su, Jinghao Sheng, Wen Lv, Guangdi Chen, Zhengping Xu

Published in: Journal of Neurology | Issue 4/2015

Abstract

The purpose of this meta-analysis was to investigate the association between progranulin polymorphism rs5848 and risk of the neurodegenerative diseases frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Published literature from PubMed and other databases were retrieved, and 16 case–control studies were identified as eligible: 5 on FTLD (1,439 cases, 4,461 controls), 5 on AD (2,502 cases, 2,162 controls), 3 on PD (1,605 cases, 1,591 controls), and 3 on ALS (663 cases, 811 controls). The pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated. We found that rs5848 was associated with an increased risk of neurodegenerative diseases in the homozygous (TT vs. CC: OR, 1.24; 95 % CI, 1.10–1.39; P < 0.001) and recessive models (TT vs. CC + CT: OR, 1.23; 95 % CI, 1.10–1.37; P < 0.001). Stratified analyses showed associations of rs5848 with increased risk of AD and PD in the homozygous and recessive models. Our data indicate that rs5848 is associated with risk of AD and PD, suggesting important roles of progranulin in neurodegenerative processes.

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Brown RC, Lockwood AH, Sonawane BR (2005) Neurodegenerative diseases: an overview of environmental risk factors. Environ Health Perspect 113:1250–1256PubMedCentralCrossRefPubMed

Lill CM, Bertram L (2011) Towards unveiling the genetics of neurodegenerative diseases. Semin Neurol 31:531–541CrossRefPubMed

Lagier-Tourenne C, Cleveland DW (2009) Rethinking ALS: the FUS about TDP-43. Cell 136:1001–1004PubMedCentralCrossRefPubMed

Rohrer JD, Guerreiro R, Vandrovcova J, Uphill J, Reiman D et al (2009) The heritability and genetics of frontotemporal lobar degeneration. Neurology 73:1451–1456PubMedCentralCrossRefPubMed

Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R et al (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442:916–919CrossRefPubMed

Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H et al (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442:920–924CrossRefPubMed

Schymick JC, Yang Y, Andersen PM, Vonsattel JP, Greenway M et al (2007) Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes. J Neurol Neurosurg Psychiatry 78:754–756PubMedCentralCrossRefPubMed

Brouwers N, Nuytemans K, van der Zee J, Gijselinck I, Engelborghs S et al (2007) Alzheimer and Parkinson diagnoses in progranulin null mutation carriers in an extended founder family. Arch Neurol 64:1436–1446CrossRefPubMed

Ward ME, Miller BL (2011) Potential mechanisms of progranulin-deficient FTLD. J Mol Neurosci 45:574–582PubMedCentralCrossRefPubMed

10.

Perry DC, Lehmann M, Yokoyama JS, Karydas A, Lee JJ et al (2013) Progranulin mutations as risk factors for Alzheimer disease. JAMA Neurol 70:774–778PubMedCentralCrossRefPubMed

11.

Cannon A, Fujioka S, Rutherford NJ, Ferman TJ, Broderick DF et al (2013) Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis. Neurology 80:1771–1777PubMedCentralCrossRefPubMed

12.

Rovelet-Lecrux A, Deramecourt V, Legallic S, Maurage CA, Le Ber I et al (2008) Deletion of the progranulin gene in patients with frontotemporal lobar degeneration or Parkinson disease. Neurobiol Dis 31:41–45CrossRefPubMed

13.

Gass J, Cannon A, Mackenzie IR, Boeve B, Baker M et al (2006) Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum Mol Genet 15:2988–3001CrossRefPubMed

14.

Cruts M, Van Broeckhoven C (2008) Loss of progranulin function in frontotemporal lobar degeneration. Trends Genet 24:186–194CrossRefPubMed

15.

Rademakers R, Eriksen JL, Baker M, Robinson T, Ahmed Z et al (2008) Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet 17:3631–3642PubMedCentralCrossRefPubMed

16.

Chang KH, Chen CM, Chen YC, Hsiao YC, Huang CC et al (2013) Association between GRN rs5848 polymorphism and Parkinson’s disease in Taiwanese population. PLoS One 8:e54448PubMedCentralCrossRefPubMed

17.

Rollinson S, Rohrer JD, van der Zee J, Sleegers K, Mead S et al (2011) No association of PGRN 3′UTR rs5848 in frontotemporal lobar degeneration. Neurobiol Aging 32:754–755CrossRefPubMed

18.

Fenoglio C, Galimberti D, Cortini F, Kauwe JS, Cruchaga C et al (2009) Rs5848 variant influences GRN mRNA levels in brain and peripheral mononuclear cells in patients with Alzheimer’s disease. J Alzheimers Dis 18:603–612PubMedCentralPubMed

19.

Jasinska-Myga B, Wider C, Opala G, Krygowska-Wajs A, Barcikowska M et al (2009) GRN 3′UTR+ 78 C>T is not associated with risk for Parkinson’s disease. Eur J Neurol 16:909–911CrossRefPubMed

20.

Del Bo R, Corti S, Santoro D, Ghione I, Fenoglio C et al (2011) No major progranulin genetic variability contribution to disease etiopathogenesis in an ALS Italian cohort. Neurobiol Aging 32:1157–1158PubMedCentralCrossRefPubMed

21.

Hayashino Y, Noguchi Y, Fukui T (2005) Systematic evaluation and comparison of statistical tests for publication bias. J Epidemiol 15:235–243CrossRefPubMed

22.

Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMed

23.

Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B57:289–300

24.

Lee MJ, Chen TF, Cheng TW, Chiu MJ (2011) rs5848 variant of progranulin gene is a risk of Alzheimer’s disease in the Taiwanese population. Neurodegener Dis 8:216–220CrossRefPubMed

25.

Galimberti D, Fenoglio C, Cortini F, Serpente M, Venturelli E et al (2010) GRN variability contributes to sporadic frontotemporal lobar degeneration. J Alzheimers Dis 19:171–177PubMed

26.

Sleegers K, Brouwers N, Maurer-Stroh S, van Es MA, Van Damme P et al (2008) Progranulin genetic variability contributes to amyotrophic lateral sclerosis. Neurology 71:253–259CrossRefPubMed

27.

Nuytemans K, Pals P, Sleegers K, Engelborghs S, Corsmit E et al (2008) Progranulin variability has no major role in Parkinson disease genetic etiology. Neurology 71:1147–1151CrossRefPubMed

28.

Kamalainen A, Viswanathan J, Natunen T, Helisalmi S, Kauppinen T et al (2013) GRN variant rs5848 reduces plasma and brain levels of granulin in Alzheimer’s disease patients. J Alzheimers Dis 33:23–27PubMed

29.

Viswanathan J, Makinen P, Helisalmi S, Haapasalo A, Soininen H et al (2009) An association study between granulin gene polymorphisms and Alzheimer’s disease in Finnish population. Am J Med Genet B Neuropsychiatr Genet 150B:747–750CrossRefPubMed

30.

Simon-Sanchez J, Seelaar H, Bochdanovits Z, Deeg DJ, van Swieten JC et al (2009) Variation at GRN 3′-UTR rs5848 is not associated with a risk of frontotemporal lobar degeneration in Dutch population. PLoS One 4:e7494PubMedCentralCrossRefPubMed

31.

Xiao S, Sato C, Kawarai T, Goodall EF, Pall HS et al (2008) Genetic studies of GRN and IFT74 in amyotrophic lateral sclerosis. Neurobiol Aging 29:1279–1282CrossRefPubMed

32.

Brouwers N, Sleegers K, Engelborghs S, Maurer-Stroh S, Gijselinck I et al (2008) Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease. Neurology 71:656–664CrossRefPubMed

33.

van der Zee J, Le Ber I, Maurer-Stroh S, Engelborghs S, Gijselinck I et al (2007) Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. Hum Mutat 28:416PubMed

34.

Slooter AJ, Cruts M, Kalmijn S, Hofman A, Breteler MM et al (1998) Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study. Arch Neurol 55:964–968CrossRefPubMed

35.

Pereson S, Wils H, Kleinberger G, McGowan E, Vandewoestyne M et al (2009) Progranulin expression correlates with dense-core amyloid plaque burden in Alzheimer disease mouse models. J Pathol 219:173–181CrossRefPubMed

36.

Dickson DW, Baker M, Rademakers R (2010) Common variant in GRN is a genetic risk factor for hippocampal sclerosis in the elderly. Neurodegener Dis 7:170–174PubMedCentralCrossRefPubMed

37.

He Z, Bateman A (2003) Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med (Berl) 81:600–612CrossRef

38.

Bateman A, Bennett HP (2009) The granulin gene family: from cancer to dementia. Bioessays 31:1245–1254CrossRefPubMed

39.

Gass J, Prudencio M, Stetler C, Petrucelli L (2012) Progranulin: an emerging target for FTLD therapies. Brain Res 1462:118–128PubMedCentralCrossRefPubMed

Title: Association of progranulin polymorphism rs5848 with neurodegenerative diseases: a meta-analysis
Authors: Yongdui Chen
Siqi Li
Liling Su
Jinghao Sheng
Wen Lv
Guangdi Chen
Zhengping Xu
Publication date: 01-04-2015
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 4/2015
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-014-7630-2

At a glance: The STEP trials

Springer Medicine

Association of progranulin polymorphism rs5848 with neurodegenerative diseases: a meta-analysis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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