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Meta-analysis of the transforming growth factor-β1 polymorphisms and susceptibility to Alzheimer’s disease

  • Dementias - Review article
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Abstract

The association between transforming growth factor-β1 (TGF-β1) gene polymorphisms and Alzheimer’s disease (AD) risk has been widely reported, but results were somewhat controversial and underpowered. To derive a more precise estimation of the relationship between TGF-β1 polymorphisms and AD risk, we conducted a meta-analysis of all available case–control studies relating the T869C and/or C-509T polymorphisms of the TGF-β1 gene to the risk of developing AD. Eligible articles were identified by search of databases including Pub Med, Web of Science, the Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and the Wan Fang (Chinese) for the period up to March 2012. Finally, a total of 14 articles were identified, 10 with 1,657 cases and 6,971 controls for T869C polymorphism and 8 with 2,618 cases and 7,473 controls for C-509T polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. Subgroup analysis was also performed by ethnicity. With respect to T869C and C-509T polymorphism, the combined results showed that there were no significant differences in genotype distribution between AD and control based on all studies. When stratifying for the race, there were also no statistically significant differences in genotype distribution between AD and controls. This meta-analysis did not provide an evidence of confirming association between the T869C and/or C-509T polymorphisms of the TGF-β1 gene and AD.

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References

  • Araria-Goumidi L, Lambert JC, Mann DM, Lendon C, Frigard B, Iwatsubo T, Cottel D, Amouyel P, Chartier-Harlin MC (2002) Association study of three polymorphisms of TGF-beta1 gene with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 73:62–64

    Article  PubMed  CAS  Google Scholar 

  • Arosio B, Bergamaschini L, Galimberti L, La Porta C, Zanetti M, Calabresi C, Scarpini E, Annoni G, Vergani C (2007) +10T/C polymorphisms in the gene of transforming growth factor-beta1 are associated with neurodegeneration and its clinical evolution. Mech Ageing Dev 128:553–557

    Article  PubMed  CAS  Google Scholar 

  • Bertram L, Tanzi RE (2008) Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 9:768–778

    Article  PubMed  CAS  Google Scholar 

  • Cacquevel M, Lebeurrier N, Che ′enne S, Vivien D (2004) Cytokines in neuroinflammation and Alzheimer’s disease. Curr Drug Targets 5:529–534

    Article  PubMed  CAS  Google Scholar 

  • Cambien F, Ricard S, Troesch A, Mallet C, Generenaz L, Evans A, Arveiler D, Luc G, Ruidavets JB, Poirier O (1996) Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Temoin de l’Infarctus du Myocarde (ECTIM) Study. Hypertension 28(5):881–887

    Article  PubMed  CAS  Google Scholar 

  • Caraci F, Battaglia G, Busceti C, Biagioni F, Mastroiacovo F, Bosco P, Drago F, Nicoletti F, Sortio MA, Copani A (2008) TGF-beta 1 protects against Abeta-neurotoxicity via the phosphatidylinositol-3-kinase pathway. Neurobiol Dis 30:234–242

    Article  PubMed  CAS  Google Scholar 

  • Caraci F, Copani A, Nicoletti F, Drago F (2010) Depression and Alzheimer’s disease: neurobiological links and common pharmacological targets. Eur J Pharmacol 626:64–71

    Article  PubMed  CAS  Google Scholar 

  • Caraci F, Battaglia G, Bruno V, Bosco P, Carbonaro V, Giuffrida ML, Drago F, Sortino MA, Nicoletti F, Copani A (2011) TGF-beta1 pathway as a new target for neuroprotection in Alzheimer’s disease. CNS Neurosci Ther 17:237–249

    Article  PubMed  CAS  Google Scholar 

  • Caraci F, Bosco P, Signorelli M, Spada RS, Cosentino FI, Toscano G, Bonforte C, Muratore S, Prestianni G, Panerai S, Giambirtone MC, Gulotta E, Romano C, Salluzzo MG, Nicoletti F, Copani A, Drago F, Aguglia E, Ferri R (2012) The CC genotype of transforming growth factor-β1 increases the risk of late-onset Alzheimer’s disease and is associated with AD-related depression. Eur Neuropsychopharmacol 22(4):281–289

    Article  PubMed  CAS  Google Scholar 

  • Castren E, Tanila H (2006) Neurotrophins and dementia—keeping in touch. Neuron 51:1–3

    Article  PubMed  CAS  Google Scholar 

  • Cousin E, Macé S, Rocher C, Dib C, Muzard G, Hannequin D, Pradier L, Deleuze JF, Génin E, Brice A, Campion D (2011) No replication of genetic association between candidate polymorphisms and Alzheimer’s disease. Neurobiol Aging 32(8):1443–1451

    Article  PubMed  CAS  Google Scholar 

  • DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114

    Article  PubMed  Google Scholar 

  • Dickson MR, Perry RT, Wiener H, Go RC (2005) Association studies of transforming growth factor-beta 1 and Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 139B:38–41

    Article  PubMed  CAS  Google Scholar 

  • DiRosa M, Dell’Ombra N, Zambito AM, Malaguarnera M, Nicoletti F, Malaguarnera L (2006) Chitotriosidase and inflammatory mediator levels in Alzheimer’s disease and cerebrovascular dementia. Eur J Neurosci 23:2648–2656

    Article  Google Scholar 

  • Flanders KC, Lippa CF, Smith TW, Pollen DA, Sporn MB (1995) Altered expression of transforming growth factor-beta in Alzheimer’s disease. Neurology 45:1561–1569

    Article  PubMed  CAS  Google Scholar 

  • Fujii D, Brissenden J, Derynck R, Francke U (1986) Transforming growth factor-beta gene maps to human chromosome 19 long arm and to mouse chromosome 7. Somat Cell Mol Genet 12:281–288

    Article  PubMed  CAS  Google Scholar 

  • Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, Carter ND, Spector TD (1999) Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 8:93–97

    Article  PubMed  CAS  Google Scholar 

  • Hamaguchi T, Okino S, Sodeyama N, Itoh Y, Takahashi A, Otomo E, Matsushita M, Mizusawa H, Yamada M (2005) Association of a polymorphism of the transforming growth factor-beta1 gene with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry 76:696–699

    Article  PubMed  CAS  Google Scholar 

  • Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356

    Article  PubMed  CAS  Google Scholar 

  • Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  • Lahiri DK, Ge YW, Maloney B (2005) Characterization of the APP proximal promoter and 50 untranslated regions: identification of cell-type specific domains and implications in APP gene expression and Alzheimer’s disease. FASEB J 19(6):653–655

    PubMed  CAS  Google Scholar 

  • Luedecking EK, DeKosky ST, Mehdi H, Ganguli M, Kamboh MI (2000) Analysis of genetic polymorphisms in the transforming growth factor-beta1 gene and the risk of Alzheimer’s disease. Hum Genet 106:565–569

    Article  PubMed  CAS  Google Scholar 

  • Luterman JD, Haroutunian V, Yemul S, Ho L, Purohit D, Aisen PS, Mohs R, Pasinetti GM (2000) Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. Arch Neurol 57:1153–1160

    Article  PubMed  CAS  Google Scholar 

  • Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  • Mosseau DD, Chapelsky S, De Crescenzo G, Kirkitadze MD, Magoon J, Inoue S, Teplow DB, O’Connor-McCourt MD (2003) A direct interaction between transforming growth factor (TGF)-betas and amyloid-beta protein affects fibrillogenesis in a TGF-beta receptor-independent manner. J Biol Chem 278:387715–438722

    Google Scholar 

  • Nishimura M, Sakamoto T, Kaji R, Kawakami H (2004) Influence of polymorphisms in the genes for cytokines and glutathione S-transferase omega on sporadic Alzheimer’s disease. Neurosci Lett 368:140–143

    Article  PubMed  CAS  Google Scholar 

  • Paul SR, Donner A (1992) Small sample performance of tests of homogeneity of odds ratios in K 2 × 2 tables. Stat Med 11:159–165

    Article  PubMed  CAS  Google Scholar 

  • Peila R, Yucesoy B, White LR, Johnson V, Kashon ML, Wu K, Petrovitch H, Luster M, Launer LJ (2007) A TGF-beta1 polymorphism association with dementia and neuropathologies: the HAAS. Neurobiol Aging 28:1367–1373

    Article  PubMed  CAS  Google Scholar 

  • Ribizzi G, Fiordoro S, Barocci S, Ferrari E, Megna M (2010) Cytokine polymorphisms and Alzheimer disease: possible associations. Neurol Sci 31:321–325

    Article  PubMed  CAS  Google Scholar 

  • Rodríguez-Rodríguez E, Sánchez-Juan P, Mateo I, Llorca J, Infante J, García-Gorostiaga I, Berciano J, Combarros O (2007) Serum levels and genetic variation of TGF-beta1 are not associated with Alzheimer’s disease. Acta Neurol Scand 116:409–412

    Article  PubMed  Google Scholar 

  • Rojo LE, Fernández JA, Maccioni AA, Jimenez JM, Maccioni RB (2008) Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer’s disease. Arch Med Res 39:1–16

    Article  PubMed  CAS  Google Scholar 

  • Schellenberg GD, Montine TJ (2012) The genetics and neuropathology of Alzheimer’s disease. Acta Neuropathol. doi:10.1007/s00401-012-0996-2

    PubMed  Google Scholar 

  • Shawkatová I, Javor J, Párnická Z, Vražda Ľ, Novák M, Buc M (2010) No association between cytokine gene polymorphism and risk of Alzheimer’s disease in Slovaks. Acta Neurobiol Exp 70:303–307

    Google Scholar 

  • Suthanthiran M, Li B, Song JO, Ding R, Sharma VK, Schwartz JE, August P (2000) Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: a novel mediator of hypertension and/or target organ damage. Proc Natl Acad Sci USA 97(7):3479–3484

    PubMed  CAS  Google Scholar 

  • Tarkowski E, Issa R, Sjogren M, Wallin A, Blennow K, Tarkowski A, Kumar P (2002) Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimer’s disease and vascular dementia. Neurobiol Aging 23:237–243

    Article  PubMed  CAS  Google Scholar 

  • van der Wal EA, Gomez-Pinilla F, Cotman CW (1993) Transforming growth factor-β1 is in plaques in Alzheimer and down pathologies. Neuro Report 4:69–72

    Google Scholar 

  • Van Oijen M, Arp PP, De Jong FJ, Hofman A, Koudstaal PJ, Uitterlinden AG, Breteler MM (2006) Polymorphisms in the interleukin 6 and transforming growth factor beta1 gene and risk of dementia. The Rotterdam Study. Neurosci Lett 402:113–117

    Article  PubMed  Google Scholar 

  • Vina J, Lloret A (2010) Why women have more Alzheimer’s disease than men: gender and mitochondrial toxicity of amyloid-beta peptide. J Alzheimers Dis 20:S527–S533

    PubMed  Google Scholar 

  • Walsh DM, Selkoe DJ (2007) A beta oligomers—a decade of discovery. J Neurochem 101:1172–1184

    Article  PubMed  CAS  Google Scholar 

  • Wang YP, Ye JP, Liu XJ, Huang SK, Chen SQ (2010) Analysis of the T869C and/or C-509T polymorphisms in the transforming growth factor-beta1 gene and the risk of Alzheimer’s disease. New Med 41:463–465 (Chinese)

    Google Scholar 

  • Wyss-Coray T (2006) Tgf-Beta pathway as a potential target in neurodegeneration and Alzheimer’s. Curr Alzheimer Res 3:191–195

    Article  PubMed  CAS  Google Scholar 

  • Ye JP, Huang SK, Chen SQ, Liu XJ, Wang YP (2010) Analysis of the T869C polymorphism in the transforming growth factor-beta1 gene and the risk of Alzheimer’s disease. Anat Res 32:93–95 (Chinese)

    CAS  Google Scholar 

  • Yokota M, Ichihara S, Lin TL, Nakashima N, Yamada Y (2000) Association of a T29→C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese. Circulation 101(24):2783–2787

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the Key Project of Wuhu Science and Technology (2009-4-2). We would like to express our gratitude to the physicians participating in this study and the editors for editing the manuscript.

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Authors and Affiliations

  1. Department of Preventive Medicine, Wannan Medical College, Wuhu, 241002, Anhui, China

    Wei-wei Chang, Yue-long Jin & Ying-shui Yao

  2. Department of Hospital Infection Management Office, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, 241000, Anhui, China

    Liu Zhang

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  1. Wei-wei Chang
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  2. Liu Zhang
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Correspondence to Ying-shui Yao.

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W. Chang and L. Zhang contributed equally to this work.

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Chang, Ww., Zhang, L., Jin, Yl. et al. Meta-analysis of the transforming growth factor-β1 polymorphisms and susceptibility to Alzheimer’s disease. J Neural Transm 120, 353–360 (2013). https://doi.org/10.1007/s00702-012-0850-7

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  • DOI: https://doi.org/10.1007/s00702-012-0850-7

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