Skip to main content
SpringerLink
Log in

Relationship between five GLUT1 gene single nucleotide polymorphisms and diabetic nephropathy: a systematic review and meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

So far, case–control studies on the association between glucose transporter 1 (GLUT1) gene single nucleotide polymorphisms (SNPs) and diabetic nephropathy (DN) have generated considerable controversy. To clarify the linkage of GLUT1 SNPs on the risk of DN, a systematic review and meta-analysis was performed. A comprehensive literature search of electronic databases was conducted to obtain relative studies. Nine case–control studies were included. Significant differences were found between XbaI SNP (rs841853) and increased risk of DN in all genetic models. Subgroup analyses for Caucasians population and DN from both type 1 and type 2 diabetes also revealed positive results. For Enh2-1 SNP (rs841847), Enh2-2 SNP (rs841848) and HaeIII SNP (rs1385129), obvious linkages were demonstrated in recessive model. However, analysis for the association between HpyCH4V SNP (rs710218) and the susceptibility of DN showed no significance. Likewise, negative outcome was also found in the assessment for the influence of XbaI or Enh2-2 SNP on the pathogenesis progress of DN. The evidence currently available shows that XbaI, Enh2 and HaeIII SNPs, but not HpyCH4V SNP, in GLUT1 gene may be genetic susceptibility to DN. However, data does not support the association between either XbaI or Enh2-2 SNP and the severity of DN.

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

Similar content being viewed by others

References

  1. Gross JL, de Azevedo MJ, Silveiro SP et al (2005) Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 28:164–176

    Article  PubMed  Google Scholar 

  2. Zhang P, Zhang X, Brown J et al (2010) Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:293–301

    Article  PubMed  Google Scholar 

  3. De Cosmo S, Prudente S, Lamacchia O et al (2011) PPARγ2 P12A polymorphism and albuminuria in patients with type 2 diabetes: a meta-analysis of case-control studies. Nephrol Dial Transplant 26:4011–4016

    Article  PubMed  Google Scholar 

  4. He Y, Fan Z, Zhang J et al (2011) Polymorphisms of eNOS gene are associated with diabetic nephropathy: a meta-analysis. Mutagenesis 26:339–349

    Article  PubMed  CAS  Google Scholar 

  5. Cui WP, Du B, Jia Y et al (2012) Is C677T polymorphism in methylenetetrahydrofolate reductase gene a risk factor for diabetic nephropathy or diabetes mellitus in Chinese population? Arch Med Res 43:42–50

    Article  PubMed  CAS  Google Scholar 

  6. Manolescu AR, Witkowska K, Kinnaird A et al (2007) Facilitated hexose transporters: new perspectives on form and function. Physiology (Bethesda) 22:234–240

    Article  CAS  Google Scholar 

  7. Baldwin SA, Lienhard GE (1989) Purification and reconstitution of glucose transporter from human erythrocytes. Methods Enzymol 174:39–50

    Article  PubMed  CAS  Google Scholar 

  8. Heilig C, Zaloga C, Lee M et al (1995) Immunogold localization of high-affinity glucose transporter isoforms in normal rat kidney. Lab Invest 73:674–684

    PubMed  CAS  Google Scholar 

  9. Heilig CW, Liu Y, England RL et al (1997) d-glucose stimulates mesangial cell GLUT1 expression and basal and IGF-I-sensitive glucose uptake in rat mesangial cells: implications of diabetic nephropathy. Diabetes 46:1030–1039

    Article  PubMed  CAS  Google Scholar 

  10. Brosius FC, Heilg CW (2005) Glucose transporters in diabetic nephropathy. Pediatr Nephrol 20:447–451

    Article  PubMed  Google Scholar 

  11. Ziyadeh FN (2004) Mediators of diabetic renal disease: the case for tgf-Beta as the major mediator. J Am Soc Nephrol 15:55–57

    Article  Google Scholar 

  12. Wang Y, Heilig KO, Minto AW et al (2010) Nephron-deficient Fvb mice develop rapidly progressive renal failure and heavy albuminuria involving excess glomerular GLUT1 and VEGF. Lab Invest 90:83–97

    Article  PubMed  CAS  Google Scholar 

  13. Studer RK, Craven PA, DeRubertis FR (1993) Role for protein kinase C in the mediation of increased fibronectin accumulation by mesangial cells grown in high-glucose medium. Diabetes 42:118–126

    Article  PubMed  CAS  Google Scholar 

  14. Pfäfflin A, Brodbeck K, Heilig CW et al (2006) Increased glucose uptake and metabolism in mesangial cells overexpressing glucose transporter 1 increases interleukin-6 and vascular endothelial growth factor production: role of AP-1 and HIF-1alpha. Cell Physiol Biochem 18:199–210

    Article  PubMed  Google Scholar 

  15. Heilig CW, Kreisberg JI, Freytag S et al (2001) Antisense GLUT1 protects mesangial cells from glucose induction of GLUT1 and fibronectin. Am J Physiol Renal Physiol 280:F657–F666

    PubMed  CAS  Google Scholar 

  16. Hsu CC, Kao WL, Steffes MW et al (2011) Genetic variation of glucose transporter-1 (GLUT1) and albuminuria in 10,278 European Americans and African Americans: a case-control study in the Atherosclerosis risk in Communities (ARIC) study. BMC Med Genet 12:16–28

    Article  PubMed  CAS  Google Scholar 

  17. Stefanidis I, Kytoudis K, Papathanasiou AA et al (2009) XbaI GLUT1 gene polymorphism and the risk of type 2 diabetes with nephropathy. Dis Markers 27:29–35

    PubMed  CAS  Google Scholar 

  18. Makni K, Jarraya F, Rebaï M et al (2008) Risk genotypes and haplotypes of the GLUT1 gene for type 2 diabetic nephropathy in the Tunisian population. Ann Hum Biol 35:490–498

    Article  PubMed  CAS  Google Scholar 

  19. Hodgkinson AD, Page T, Millward BA et al (2005) A novel polymorphism in the 5′ flanking region of the glucose transporter (GLUT1) gene is strongly associated with diabetic nephropathy in patients with Type 1 diabetes mellitus. J Diabetes Complicat 19:65–69

    Article  PubMed  CAS  Google Scholar 

  20. Ng DP, Canani L, Araki S et al (2002) Minor effect of GLUT1 polymorphisms on susceptibility to diabetic nephropathy in type 1 diabetes. Diabetes 51:2264–2269

    Article  PubMed  CAS  Google Scholar 

  21. Hodgkinson AD, Millward BA, Demaine AG (2001) Polymorphisms of the glucose transporter (GLUT1) gene are associated with diabetic nephropathy. Kidney Int 59:985–989

    Article  PubMed  CAS  Google Scholar 

  22. Tarnow L, Grarup N, Hansen T et al (2001) Diabetic microvascular complications are not associated with two polymorphisms in the GLUT-1 and PC-1 genes regulating glucose metabolism in Caucasian type 1 diabetic patients. Nephrol Dial Transplant 16:1653–1656

    Article  PubMed  CAS  Google Scholar 

  23. Liu ZH, Guan TJ, Chen ZH et al (1999) Glucose transporter (GLUT1) allele (XbaI-) associated with nephropathy in non-insulin-dependent diabetes mellitus. Kidney Int 55:1843–1848

    Article  PubMed  CAS  Google Scholar 

  24. Gutierrez C, Vendrell J, Pastor R et al (1998) GLUT1 gene polymorphism in non-insulin-dependent diabetes mellitus: genetic susceptibility relationship with cardiovascular risk factors and microangiopathic complications in a Mediterranean population. Diabetes Res Clin Pract 41:113–120

    Article  PubMed  CAS  Google Scholar 

  25. Grzeszczak W, Moczulski DK, Zychma M et al (2001) Role of GLUT1 gene in susceptibility to diabetic nephropathy in type 2 diabetes. Kidney Int 59:631–636

    Article  PubMed  CAS  Google Scholar 

  26. Lau J, Ioannidis JP, Schmid CH (1998) Summing up evidence: one answer is not always enough. Lancet 351:570–573

    Article  Google Scholar 

  27. Lau J, Ioannidis JP, Schmid CH (1997) Qauntitative synthesis in systematic reviews. Ann Intern Med 127:820–826

    PubMed  CAS  Google Scholar 

  28. Zintzaras E, Ioannidis JP (2005) HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics 21:3672–3673

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  30. Harel Z, Gilbert C, Wald R, et al. (2012) The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. BMJ [Epub ahead of print]

  31. Leucht S, Corves C, Arbter D et al (2009) Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373:31–41

    Article  PubMed  CAS  Google Scholar 

  32. Wang Y, Chen J, Wang Y et al (2011) A meta-analysis of the clinical remission rate and long-term efficacy of tonsillectomy in patients with IgA nephropathy. Nephrol Dial Transplant 26:1923–1931

    Article  PubMed  CAS  Google Scholar 

  33. Mueckler M, Caruso C, Baldwin SA et al (1985) Sequence and structure of a human glucose transporter. Science 229:941–945

    Article  PubMed  CAS  Google Scholar 

  34. Hruz PW, Mueckler MM (2001) Structural analysis of the GLUT1 facilitative glucose transporter (review). Mol Membr Biol 18:183–193

    Article  PubMed  CAS  Google Scholar 

  35. Arnoni CP, Lima C, Cristovam PC et al (2009) Regulation of glucose uptake in mesangial cells stimulated by high glucose: role of angiotensin II and insulin. Exp Biol Med (Maywood) 234:1095–1101

    Article  CAS  Google Scholar 

  36. Sokolovska J, Isajevs S, Sugoka O et al (2010) Influence of metformin on GLUT1 gene and protein expression in rat streptozotocin diabetes mellitus model. Arch Physiol Biochem 116:137–145

    Article  PubMed  CAS  Google Scholar 

  37. Heilig CW, Concepcion LA, Riser BL et al (1995) Overexpression of glucose transporters in rat mesangial cells cultured in a normal glucose milieu mimics the diabetic phenotype. J Clin Invest 96:1802–1814

    Article  PubMed  CAS  Google Scholar 

  38. Wang Y, Heilig K, Saunders T et al (2010) Transgenic overexpression of GLUT1 in mouse glomeruli produces renal disease resembling diabetic glomerulosclerosis. Am J Physiol Renal Physiol 299:99–111

    Article  Google Scholar 

  39. Tao T, Tanizawa Y, Matsutani A et al (1995) HepG2/erythrocyte glucose transporter (GLUT1) gene in NIDDM: a population association study and molecular scanning in Japanese subjects. Diabetologia 38:942–947

    Article  PubMed  CAS  Google Scholar 

  40. Baroni MG, D’Andrea MP, Capici F et al (1998) High frequency of polymorphism but no mutations found in the GLUT1 glucose transporter gene in NIDDM and familial obesity by SSCP analysis. Hum Genet 102:479–482

    Article  PubMed  CAS  Google Scholar 

  41. Lefrançois-Martinez AM, Martinez A, Antoine B et al (1995) Upstream stimulatory factor proteins are major components of the glucose response complex of the L-type pyruvate kinase gene promoter. J Biol Chem 270:2640–2643

    Article  PubMed  Google Scholar 

  42. Gosek K, Moczulski D, Zukowska-Szczechowska E et al (2005) C-106T polymorphism in promoter of aldose reductase gene is a risk factor for diabetic nephropathy in type 2 diabetes patients with poor glycemic control. Nephron Exp Nephrol 99:63–67

    Article  Google Scholar 

  43. Sivenius K, Niskanen L, Voutilainen-Kaunisto R et al (2004) Aldose reductase gene polymorphisms and susceptibility to microvascular complications in Type 2 diabetes. Diabet Med 21:1325–1533

    Article  PubMed  CAS  Google Scholar 

  44. Zhao HL, Tong PC, Lai FM et al (2004) Association of glomerulopathy with the 5′-end polymorphism of the aldose reductase gene and renal insufficiency in type 2 diabetic patients. Diabetes 53:2984–2991

    Article  PubMed  CAS  Google Scholar 

  45. Costa GC, Alcantara LC, Azevedo R et al (2010) Frequency distribution of XbaIG > T and HaeIII T > C GLUT1 polymorphisms among different Brazilian ethnic groups. Mol Biol Rep 37:75–79

    Article  PubMed  CAS  Google Scholar 

  46. Li SR, Oelbaum RS, Bouloux PM et al (1990) Restriction site polymorphisms at the human HepG2 glucose transporter gene locus in Caucasian and west Indian subjects with non-insulin-dependent diabetes mellitus. Hum Hered 40:38–44

    Article  PubMed  CAS  Google Scholar 

  47. Zintzaras E, Stefanidis I (2005) Association between the GLUT1 gene polymorphism and the risk of diabetic nephropathy: a meta-analysis. J Hum Genet 50:84–91

    Article  PubMed  Google Scholar 

  48. Mooyaart AL, Valk EJ, van Es LA et al (2011) Genetic associations in diabetic nephropathy: a meta-analysis. Diabetologia 54:544–553

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to express our gratitude to all the physicians participating in this work.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Nephrology, Second Hospital, Jilin University, 218 Ziqiang Street, Changchun, 130041, Jilin, China

    Wenpeng Cui, Wenhua Zhou, Ye Jia, Guangdong Sun, Jing Sun, Dongmei Zhang, Hang Yuan, Feng Xu, Xuehong Lu, Ping Luo & Lining Miao

  2. Department of Cardiology, First Hospital, Jilin University, Changchun, 130031, Jilin, China

    Bing Du

Authors
  1. Wenpeng Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bing Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wenhua Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ye Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guangdong Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jing Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dongmei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hang Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Feng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xuehong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ping Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Lining Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lining Miao.

Additional information

Wenpeng Cui and Bing Du contributed equally to this work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cui, W., Du, B., Zhou, W. et al. Relationship between five GLUT1 gene single nucleotide polymorphisms and diabetic nephropathy: a systematic review and meta-analysis. Mol Biol Rep 39, 8551–8558 (2012). https://doi.org/10.1007/s11033-012-1711-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1711-z

Keywords

Search

Navigation