Skip to main content

Advertisement

SpringerLink
Log in

Relationship between the FAS gene A-670G polymorphism and Alzheimer’s disease: a meta-analysis

  • Review
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Backgrounds and aims

The pathogenetic mechanism of Alzheimer’s disease (AD) is still unknown; however, gene polymorphism may play a critical role in the pathogenesis of AD. The aim of this meta-analysis was to evaluate the association between FAS gene A-670G polymorphism and AD.

Methods

We searched all related subjects in PubMed, Embase, Cochrane Library, SinoMed, and the China Knowledge Resource Integrated Database and identified seven studies reporting a relationship between the A-670G polymorphism in the FAS gene and AD.

Results

A total of 1512 cases and 1707 controls were included in the seven studies. The meta-analyses results suggested no significant association between the A-670G polymorphism and AD in any genetic models. When a subgroup analysis was conducted by ethnicity, the A-670G polymorphism was also not relevant to AD. However, when stratified by age, the GG genotype increased the risk of early-onset AD. We also found that the A-670G polymorphism was related to patients with AD who carried the apolipoprotein-E ε4 allele in three genetic models.

Conclusions

To sum up, our data suggested that the FAS gene A-670G polymorphism may not be associated with AD. When a subgroup analysis was conducted by ethnicity, the A-670G polymorphism was also not related with AD in Asian and Caucasian population. However, the FAS-670 GG genotype may increase the risk of AD in the younger population (age, ≤65 years). Furthermore, we found that the A-670G polymorphism was related to patients with AD who carried the APOE4 allele in dominant, allele and homozygous models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

CI:

Confidence interval

OR:

Odds ratio

AD:

Alzheimer’s disease

APOE4:

Apolipoprotein-E ε4

References

  1. Tol J, Roks G, Slooter AJ, van Duijn CM (1999) Genetic and environmental factors in Alzheimer’s disease. Rev Neurol (Paris) 155(Suppl 4):S10–S16

    Google Scholar 

  2. Yoshizawa T, Yamakawa-Kobayashi K, Komatsuzaki Y, Arinami T, Oguni E, Mizusawa H et al (1994) Dose-dependent association of apolipoprotein E allele epsilon 4 with late-onset, sporadic Alzheimer’s disease. Ann Neurol 36:656–659

    Article  CAS  PubMed  Google Scholar 

  3. Roses AD, Saunders AM (1994) APOE is a major susceptibility gene for Alzheimer’s disease. Curr Opin Biotechnol 5:663–667

    Article  CAS  PubMed  Google Scholar 

  4. Daw EW, Payami H, Nemens EJ, Nochlin D, Bird TD, Schellenberg GD et al (2000) The number of trait loci in late-onset Alzheimer disease. Am J Hum Genet 66:196–204

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Su JH, Anderson AJ, Cribbs DH, Tu C, Tong L, Kesslack P et al (2003) Fas and Fas ligand are associated with neuritic degeneration in the AD brain and participate in beta-amyloid-induced neuronal death. Neurobiol Dis 12:182–193

    Article  CAS  PubMed  Google Scholar 

  6. Dang TN, Arseneault M, Murthy V, Ramassamy C (2010) Potential role of acrolein in neurodegeneration and in Alzheimer’s disease. Curr Mol Pharmacol 3:66–78

    Article  PubMed  Google Scholar 

  7. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA et al (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403:98–103

    Article  CAS  PubMed  Google Scholar 

  8. Su JH, Anderson AJ, Cummings BJ, Cotman CW (1994) Immunohistochemical evidence for apoptosis in Alzheimer’s disease. NeuroReport 5:2529–2533

    Article  CAS  PubMed  Google Scholar 

  9. Richartz E, Noda S, Schott K, Gunthner A, Lewczuk P, Bartels M (2002) Increased serum levels of CD95 in Alzheimer’s disease. Dement Geriatr Cogn Disord 13:178–182

    Article  CAS  PubMed  Google Scholar 

  10. Martinez M, Fernandez-Vivancos E, Frank A, De la Fuente M, Hernanz A (2000) Increased cerebrospinal fluid fas (Apo-1) levels in Alzheimer’s disease. Relationship with IL-6 concentrations. Brain Res 869:216–219

    Article  CAS  PubMed  Google Scholar 

  11. de la Monte SM, Sohn YK, Wands JR (1997) Correlates of p53- and Fas (CD95)-mediated apoptosis in Alzheimer’s disease. J Neurol Sci 152:73–83

    Article  PubMed  Google Scholar 

  12. Nishimura T, Akiyama H, Yonehara S, Kondo H, Ikeda K, Kato M et al (1995) Fas antigen expression in brains of patients with Alzheimer-type dementia. Brain Res 695:137–145

    Article  CAS  PubMed  Google Scholar 

  13. Andreoli V, Nicoletti G, Romeo N, Condino F, La Russa A, Liguori M et al (2007) Fas antigen and sporadic Alzheimer’s disease in Southern Italy: evaluation of two polymorphisms in the TNFRSF6 gene. Neurochem Res 32:1445–1449

    Article  CAS  PubMed  Google Scholar 

  14. Chiappelli M, Nasi M, Cossarizza A, Porcellini E, Tumini E, Pinti M et al (2006) Polymorphisms of fas gene: relationship with Alzheimer’s disease and cognitive decline. Dement Geriatr Cogn Disord 22:296–300

    Article  CAS  PubMed  Google Scholar 

  15. Feuk L, Prince JA, Breen G, Emahazion T, Carothers A, St Clair D et al (2000) apolipoprotein-E dependent role for the FAS receptor in early onset Alzheimer’s disease: finding of a positive association for a polymorphism in the TNFRSF6 gene. Hum Genet 107:391–396

    Article  CAS  PubMed  Google Scholar 

  16. He XM, Zhang ZX, Zhang JW, Zhou YT, Tang MN, Wu CB et al (2006) The Fas gene A-670G polymorphism is not associated with sporadic Alzheimer disease in a Chinese Han population. Brain Res 1082:192–195

    Article  CAS  PubMed  Google Scholar 

  17. Rosenmann H, Meiner Z, Kahana E, Aladjem Z, Friedman G, Ben-Yehuda A et al (2004) The Fas promoter polymorphism at position -670 is not associated with late-onset sporadic Alzheimer’s disease. Dement Geriatr Cogn Disord 17:143–146

    Article  CAS  PubMed  Google Scholar 

  18. Theuns J, Feuk L, Dermaut B, Del-Favero J, Roks G, Van den Bossche D et al (2001) The TNFRSF6 gene is not implicated in familial early-onset Alzheimer’s disease. Hum Genet 108:552–553

    Article  CAS  PubMed  Google Scholar 

  19. S-l Ma, Tang NLS, Lui VWC, Tam CWC, Lui VWC, Chiu HFK (2006) Lack of association between tumour necrosis factor receptor superfamily gene polymorphisms and the risk of Alzheimer’s disease in a Chinese population. Hong Kong J Psychiatry 16:128–131

    Google Scholar 

  20. Guo J, Jin M, Zhang M, Chen K (2012) A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies. PLoS One 7:e30585

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Kawai M, Kalaria RN, Harik SI, Perry G (1990) The relationship of amyloid plaques to cerebral capillaries in Alzheimer’s disease. Am J Pathol 137:1435–1446

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Yu W, Bonnet M, Farso M, Ma K, Chabot JG, Martin E et al (2014) The expression of apoptosis inducing factor (AIF) is associated with aging-related cell death in the cortex but not in the hippocampus in the TgCRND8 mouse model of Alzheimer’s disease. BMC Neurosci 15:73

    Article  PubMed Central  PubMed  Google Scholar 

  26. Louneva N, Cohen JW, Han LY, Talbot K, Wilson RS, Bennett DA et al (2008) Caspase-3 is enriched in postsynaptic densities and increased in Alzheimer’s disease. Am J Pathol 173:1488–1495

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Gervais FG, Xu D, Robertson GS, Vaillancourt JP, Zhu Y, Huang J et al (1999) Involvement of caspases in proteolytic cleavage of Alzheimer’s amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell 97:395–406

    Article  CAS  PubMed  Google Scholar 

  28. van Duijn CM, de Knijff P, Cruts M, Wehnert A, Havekes LM, Hofman A et al (1994) Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer’s disease. Nat Genet 7:74–78

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The article does not contain any studies with human participants performed by any of the authors.

Author information

Author notes

    Authors and Affiliations

    1. Nanjing Medical University, Nanjing, 210029, China

      Jinlong Zhu

    2. Department of Neurology, The Jintan Hospital Affiliated to Jiangsu University, Changzhou, 213200, China

      Jianhua Su

    3. Department of Orthopaedic Trauma, Changzhou Second People’s Hospital, Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China

      Ruiping Liu

    4. Central Laboratory, Changzhou Second People’s Hospital, Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China

      Ruiping Liu

    5. Department of Cerebral Surgery, Changzhou Second People’s Hospital, Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China

      Jinsong Yang

    Authors
    1. Jinlong Zhu
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jianhua Su
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ruiping Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Jinsong Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Ruiping Liu or Jinsong Yang.

    Additional information

    Jinlong Zhu and Jianhua Su contributed equally to this study.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zhu, J., Su, J., Liu, R. et al. Relationship between the FAS gene A-670G polymorphism and Alzheimer’s disease: a meta-analysis. Aging Clin Exp Res 27, 563–571 (2015). https://doi.org/10.1007/s40520-015-0351-2

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40520-015-0351-2

    Keywords

    Search

    Navigation