Skip to main content

Advertisement

SpringerLink
Log in

Associations of polymorphisms in the candidate genes for Alzheimer’s disease BIN1, CLU, CR1 and PICALM with gestational diabetes and impaired glucose tolerance

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is the most common type of dementia, with a prevalence that is rising every year. AD is associated with type 2 diabetes mellitus (T2DM) and insulin resistance, and is therefore sometimes called “type 3 diabetes mellitus”. The aim of this study was to examine whether the variants of some candidate genes involved in the development of AD, namely BIN1 (rs744373), CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179), are related to several disorders of glucose metabolism—gestational diabetes (GDM), T2DM and impaired glucose tolerance (IGT). Our study included 550 women with former GDM and 717 control women, 392 patients with T2DM and 180 non-diabetic controls, and 117 patients with IGT and 630 controls with normal glucose tolerance. Genotyping analysis was performed using specially-designed TaqMan assays. No significant associations of the genetic variants rs744373 in BIN1, rs11136000 in CLU, or rs3818361 in CR1 were found with GDM, T2DM or IGT, but rs3851179 in PICALM was associated with an increased risk of GDM. The frequency of the AD risk-associated C allele was significantly higher in the GDM group compared to controls: OR 1.21; 95% CI (1.03–1.44). This finding was not apparent in T2DM and IGT; conversely, the C allele of the PICALM SNP was protective for IGT: OR 0.67; 95% CI (0.51–0.89). This study demonstrates an association between PICALM rs3851179 and GDM as well as IGT. However, elucidation of the possible role of this gene in the pathogenesis of GDM requires further independent studies.

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

Similar content being viewed by others

References

  1. Prince M, Albanese E, Guerchet M, Prina M (2014) World Alzheimer report 2014. Alzheimer’s Disease International, London, England

  2. Pimplikar SW (2009) Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. Int J Biochem Cell Biol 41(6):1261–1268

    Article  CAS  PubMed  Google Scholar 

  3. Ballatore C, Lee VM, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 8(9):663–672

    Article  CAS  PubMed  Google Scholar 

  4. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease-is type 3 diabetes? J Alzheimers Dis 7(1):63–80

    Article  CAS  PubMed  Google Scholar 

  5. de la Monte SM, Wands JR (2005) Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimers Dis 7(1):45–61

    Article  PubMed  Google Scholar 

  6. Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM (2005) Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reductions in acetylcholine. J Alzheimers Dis 8(3):247–268

    Article  CAS  PubMed  Google Scholar 

  7. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—is the type 3 diabetes? J Alzheimers Dis 7(1):63–80

    Article  CAS  PubMed  Google Scholar 

  8. Waring SC, Rosenberg RN (2008) Genome-wide association studies in Alzheimer disease. Arch Neurol 65(3):329–334

    Article  PubMed  Google Scholar 

  9. Lambert JCh, Heath S, Even G et al (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet 41(10):1094–1099

    Article  CAS  PubMed  Google Scholar 

  10. Seshadri S, Fitzpatrick AL, Ikram MA et al (2010) Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303(18):1832–1840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kamboh MI, Demirci FY, Wang X et al (2012) Genome-wide association study of Alzheimer’s disease. Transl Psychiatry 2(5):e117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vilatela MEA, López-López M, Yescas-Gómez P (2012) Genetics of Alzheimer’s disease. Arch Res Med 43(8):622–631

    Article  Google Scholar 

  13. Harold D, Abraham R, Hollingworth P et al (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41(10):1088–1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Scotland PB, Heath JL, Conway AE, Porter NB, Armstrong MB, Walker JA, Klebig ML, Lavau CP, Wechsler DS (2012) The PICALM protein plays a key role in iron homeostasis and cell proliferation. PLoS ONE 7(8):e44252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Crespo AC, Silva B, Marques L, Marcelino E, Maruta C, Costa S, Timoteo A, Vilares A, Couto FS, Faustino P, Correira AP, Verdelho A, Porto G, Guerreiro M, Herrero A, Costa C, de Mendoca A, Costa L, Martins M (2014) Genetic and biochemical markers in patients with Alzheimer’s disease support a concentrated systemic iron homeostasis dysregulation. Neurobiol Aging 35(4):777–785

    Article  CAS  PubMed  Google Scholar 

  16. Bartzokis G, Tishler TA (2000) MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer’s and Hungtington’s disease. Cell Mol Biol 46(4):821–833

    CAS  PubMed  Google Scholar 

  17. Amiri FN, Basirat Z, Omidvar S, Sharbatdaran M, Tilaki KH, Pouramir M (2013) Comparison of the serum iron, ferritin levels and total iron-binding capacity between pregnant women with and without gestational diabetes. J Nat Sci Biol Med 4(2):302–305

    Article  PubMed  PubMed Central  Google Scholar 

  18. Khambalia AZ, Aimone A, Nagubandi P, Roberts CL, McElduff A, Morris JM, Powell KL, Tasevski V, Nassar N (2016) High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: a prospective study and systematic review. Diabet Med 33(9):1211–1221

    Article  CAS  PubMed  Google Scholar 

  19. Yang A, Zhao J, Lu M, Gu Y, Zhu Y, Chen D, Fu J (2016) Expression of hepcidin and ferroportin in the placenta, and ferritin and transferrin receptor 1 levels in maternal and umbilical cord blood in pregnant women with and without gestational diabetes. Int J Environ Res Public 13(8):766

    Article  Google Scholar 

  20. Mercer JL, Argus JP, Crabtree DM, Keenan MM, Wilks MQ, Chi JT, Bensinger SJ, Lavau CP, Wechsler DS (2015) Modulation of PICALM levels perturbs cellular cholesterol homeostasis. PLoS ONE 10(6):e0129776

    Article  PubMed  PubMed Central  Google Scholar 

  21. McFall GP, Wiebe SA, Vergote D, Anstey KJ, Dixon RA (2015) Alzheimer’s genetic risk intensifies neurocognitive slowing associated with diabetes in non-demented older adults. Alzheimers Dement 1(4):395–402

    Google Scholar 

Download references

Acknowledgements

Supported by the Ministry of Health, Czech Republic—conceptual development of a research organization (Institute of Endocrinology—EU, 00023761) and by IGA NT/13543-4 Ministry of Health, Czech Republic.

Author information

Authors and Affiliations

  1. Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic

    Gabriela Vacínová, D. Vejražková, P. Lukášová, O. Lischková, K. Dvořáková, J. Včelák, B. Bendlová & M. Vaňková

  2. Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Prague, Czech Republic

    Gabriela Vacínová

  3. Thomayer Hospital, Prague, Czech Republic

    R. Rusina

  4. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital in Prague, Charles University in Prague, Prague, Czech Republic

    R. Rusina

  5. Faculty of Humanities, Charles University in Prague, Prague, Czech Republic

    I. Holmerová & H. Vaňková

  6. Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

    H. Vaňková

Authors
  1. Gabriela Vacínová
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Vejražková
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Lukášová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. Lischková
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Dvořáková
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Rusina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I. Holmerová
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H. Vaňková
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. Včelák
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. B. Bendlová
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M. Vaňková
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriela Vacínová.

Ethics declarations

Conflict of interest

There is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vacínová, G., Vejražková, D., Lukášová, P. et al. Associations of polymorphisms in the candidate genes for Alzheimer’s disease BIN1, CLU, CR1 and PICALM with gestational diabetes and impaired glucose tolerance. Mol Biol Rep 44, 227–231 (2017). https://doi.org/10.1007/s11033-017-4100-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-017-4100-9

Keywords

Search

Navigation