Skip to main content

Advertisement

SpringerLink
Log in

Genetic Association of SLC2A14 Polymorphism with Alzheimer’s Disease in a Han Chinese Population

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Glucose uptake and metabolism are impaired in Alzheimer’s disease (AD) brain, which appear to be a cause, rather than a consequence of neurodegeneration. Recently, the gene of the 14th isoform of subfamily A of solute carrier family 2 (SLC2A14), encoding glucose transporter 14 (GLUT14), was identified for the association in vivo with AD pathology of Tau, and rs10845990 within SLC2A14 showed association with AD in Caucasians. In order to evaluate the involvement of the SLC2A14 polymorphism in the risk of developing late-onset Alzheimer’s disease (LOAD) in Chinese, we performed an independent case–control association study in a Han Chinese population (597 LOAD cases and 605 healthy controls). There were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P = 0.015, allele P = 0.039). The G-carrying genotype (GT + GG) individuals showed a 1.41-fold increased risk compared with the TT genotype carriers (odds ratio (OR) = 1.41, 95 % confidence interval (CI) = 1.11–1.79, P = 0.005, Power = 83.6 %). After stratification by ApoE ε4-carrying status, rs10845990 polymorphism was only significantly associated with LOAD in non-ApoE ε4 allele carriers (P < 0.001). Multivariate logistic regression analysis also conferred this positive association between the SNP rs10845990 and LOAD in the dominant and additive model after adjustment for age, gender, and the ApoE ε4 carrier status. These results suggested that SLC2A14 polymorphism has a possible role in changing the genetic susceptibility to LOAD in a Han Chinese population.

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

References

  • Benson DF, Kuhl DE, Hawkins RA, Phelps ME, Cummings JL, Tsai SY (1983) The fluorodeoxyglucose 18 F scan in Alzheimer’s disease and multi-infarct dementia. Arch Neurol 40:711–714

    Article  PubMed  CAS  Google Scholar 

  • De Santi S, de Leon MJ, Rusinek H, Convit A, Tarshish CY, Roche A, Tsui WH, Kandil E, Boppana M, Daisley K, Wang GJ, Schlyer D, Fowler J (2001) Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging 22:529–539

    Article  PubMed  Google Scholar 

  • Deng Y, Li B, Liu Y, Iqbal K, Grundke-Iqbal I, Gong CX (2009) Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: implication for Alzheimer’s disease. Am J Pathol 175(5):2089–2098

    Article  PubMed  CAS  Google Scholar 

  • Dias-Santagata D, Fulga TA, Duttaroy A, Feany MB (2007) Oxidative stress mediates tau-induced neurodegeneration in Drosophila. J Clin Invest 117:236–245

    Article  PubMed  CAS  Google Scholar 

  • Gibson GE (2002) Interactions of oxidative stress with cellular calcium dynamics and glucose metabolism in Alzheimer’s disease. Free Radic Biol Med 32(11):1061–1070

    Article  PubMed  CAS  Google Scholar 

  • Gong CX, Liu F, Grundke-Iqbal I, Iqbal K (2006) Impaired brain glucose metabolism leads to Alzheimer neurofibrillary degeneration through a decrease in tau O-GlcNAcylation. J Alzheimer’s Dis 9(1):1–12

    CAS  Google Scholar 

  • Hoyer S (2000) Brain glucose and energy metabolism abnormalities in sporadic Alzheimer disease. Causes and consequences: an update. Exp Gerontol 35(9–10):1363–1372

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S (2004) Causes and consequences of disturbances of cerebral glucose metabolism in sporadic Alzheimer disease: therapeutic implications. Adv Exp Med Biol 541:135–152

    Article  PubMed  CAS  Google Scholar 

  • Kalaria RN (1999) The blood–brain barrier and cerebrovascular pathology in Alzheimer’s disease. Ann N Y Acad Sci 893:113–125

    Article  PubMed  CAS  Google Scholar 

  • Liang WS, Reiman EM, Valla J, Dunckley T, Beach TG, Grover A, Niedzielko TL, Schneider LE, Mastroeni D, Caselli R, Kukull W, Morris JC, Hulette CM, Schmechel D, Rogers J, Stephan DA (2008) Alzheimer’s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci U S A 105(11):4441–4446

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Liu F, Iqbal K, Grundke-Iqbal I, Gong CX (2008) Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett 582(2):359–364

    Article  PubMed  CAS  Google Scholar 

  • Mamelak M (2007) Alzheimer’s disease, oxidative stress and gammahydroxybutyrate. Neurobiol Aging 28(9):1340–1360

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS, Reagan LP (2004) Glucose transporter expression in the central nervous system: relationship to synaptic function. Eur J Pharmacol 490(1–3):13–24

    Article  PubMed  CAS  Google Scholar 

  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944

    Article  PubMed  CAS  Google Scholar 

  • Piert M, Koeppe RA, Giordani B, Berent S, Kuhl DE (1996) Diminished glucose transport and phosphorylation in Alzheimer’s disease determined by dynamic FDG-PET. J Nucl Med 37:201–208

    PubMed  CAS  Google Scholar 

  • Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362:329–344

    Article  PubMed  CAS  Google Scholar 

  • Rhead B, Karolchik D, Kuhn RM, Hinrichs AS, Zweig AS, Fujita PA, Diekhans M, Smith KE, Rosenbloom KR, Raney BJ, Pohl A, Pheasant M, Meyer LR, Learned K, Hsu F, Hillman-Jackson J, Harte RA, Giardine B, Dreszer TR, Clawson H, Barber GP, Haussler D, Kent WJ (2010) The UCSC Genome Browser database: update 2010. Nucleic Acids Res 38(Database issue):D613–619

    Article  PubMed  CAS  Google Scholar 

  • Shulman JM, Chipendo P, Chibnik LB, Aubin C, Tran D, Keenan BT, Kramer PL, Schneider JA, Bennett DA, Feany MB, De Jager PL (2011) Functional screening of Alzheimer pathology genome-wide association signals in Drosophila. Am J Hum Genet 88(2):232–238

    Article  PubMed  CAS  Google Scholar 

  • Simpson IA, Chunda KR, Davies-Hill T, Honer WG, Davies P (1994) Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer’s disease. Ann Neurol 35:546–551

    Article  PubMed  CAS  Google Scholar 

  • Strazielle C, Jazi R, Verdier Y, Qian S, Lalonde R (2009) Regional brain metabolism with cytochrome c oxidase histochemistry in a PS1/A246E mouse model of autosomal dominant Alzheimer’s disease: correlations with behavior and oxidative stress. Neurochem Int 55(8):806–814

    Article  PubMed  CAS  Google Scholar 

  • Wu XH, Freeze HH (2002) GLUT14, a duplicon of GLUT3, is specifically expressed in testis as alternative splice forms. Genomics 80:553–557

    Article  PubMed  CAS  Google Scholar 

  • Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S, Hodge CL, Haase J, Janes J, Huss JW 3rd, Su AI (2009) BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 10:R130

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to all of the subjects who kindly agreed to participate in this study. The study was supported by grants from the National Natural Science Foundation of China (81000544, 81171209), the Shandong Provincial Natural Science Foundation of China (ZR2010HQ004, ZR2011HZ001), the Medicine and Health Science Technology Development Project of Shandong Province (2011WSA02018, 2011WSA02020), and the Shandong Provincial Outstanding Medical Academic Professional Program.

Conflict of interests

All the authors declare that they have no conflict of interests related with this work.

Author information

Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, 266071, People’s Republic of China

    Wei Wang, Jin-Tai Yu, Wei Zhang, Zhong-Chen Wu, Qun Zhang & Lan Tan

  2. Department of Geratology, Qingdao Mental Health Center, Qingdao, 266031, China

    Wei-Zhen Cui

Authors
  1. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-Tai Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei-Zhen Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhong-Chen Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lan Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jin-Tai Yu or Lan Tan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, W., Yu, JT., Zhang, W. et al. Genetic Association of SLC2A14 Polymorphism with Alzheimer’s Disease in a Han Chinese Population. J Mol Neurosci 47, 481–484 (2012). https://doi.org/10.1007/s12031-012-9748-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-012-9748-y

Keywords

Search

Navigation