Skip to main content
SpringerLink
Log in

Gene polymorphism of vascular endothelial growth factor −1154 G>A is associated with hypertensive nephropathy in a Hispanic population

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The aim of this study was to determine the association between hypertensive nephropathy and gene polymorphisms of vascular endothelial growth factor (VEGF) in a self-reported Hispanic patient group. A total of 155 Hispanic living kidney donors as controls and a total of 86 Hispanic kidney transplant patients, whose renal failure was attributed to hypertensive nephropathy after ruling out diabetes mellitus or other causes, were genotyped for four different single nucleotide polymorphisms of VEGF: −2578 C>A (rs699947), −1154 G>A (rs1570360), −460 C>T (rs833061), and +936 C>T (rs3025039). The homozygous mutant type (AA) of VEGF −1154 G>A (rs1570360) was found with significantly higher frequency in the hypertensive nephropathy patients than in controls. On the other hand, homozygous wild type (GG) was found less frequently in the hypertensive nephropathy patient group than in the control group. Linkage disequilibrium (LD) analyses revealed a high degree of LD among VEGF −2578 C>A (rs699947), VEGF −1154 G>A (rs1570360), and VEGF −460 C>T (rs833061). The haplotype analysis revealed that two haplotypes, CGTC and CATC (in the order of VEGF −2578 C>A (rs699947), −1154 G>A (1570360), −460 C>T (rs833061), and +936 C>T (3025039)), were significantly associated with hypertensive nephropathy in Hispanic patients. Hence, the −1154 G>A polymorphism (rs1570360) and two haplotypes (CGTC and CATC) of VEGF appear to be associated with hypertensive nephropathy in Hispanic patients who developed end-stage renal disease requiring kidney transplant.

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. Hamman RF, Marshall JA, Baxter J, Kahn LB, Mayer EJ, Orleans M, Murphy JR, Lezotte DC (1989) Methods and prevalence of non-insulin-dependent diabetes mellitus in a biethnic Colorado population: The San Luis Valley Diabetes Study. Am J Epidemiol 129:295–311

    PubMed  CAS  Google Scholar 

  2. Flegal KM, Ezzati TM, Harris MI, Haynes SG, Juarez RZ, Knowler WC, Perez-Stable EJ, Stern MP (1991) Prevalence of diabetes in Mexican Americans, Cubans, Puerto Ricans from the Hispanic Health, Nutrition Examination Survey, 1982–1984. Diabetes Care 14:628–638

    Article  PubMed  CAS  Google Scholar 

  3. Haffner SM, Hazuda HP, Mitchell BD, Patterson JK, Stern MP (1991) Increased incidence of type II diabetes mellitus in Mexican Americans. Diabetes Care 14:102–108

    Article  PubMed  CAS  Google Scholar 

  4. Russo C, Jin Z, Homma S, Rundek T, Elkind MSV, Sacco RL, Tullio MRD (2010) Race/ethnic disparities in left ventricular diastolic function in a triethnic community cohort. Am Heart J 160:152–158

    Article  PubMed  Google Scholar 

  5. Press R, Carrasquillo O, Nickolas T, Radhakrishnan J, Shea S, Barr RG (2005) Race/ethnicity, poverty status, and renal transplant outcomes. Transplantation 80(7):917–924

    Article  PubMed  Google Scholar 

  6. Feyssa E, Jones-Burton C, Ellison G, Philosophe B, Howell C (2009) Racial/ethnic disparity in kidney transplantation outcomes: influence of donor and recipient characteristics. J Natl Med Assoc 101(2):111–115

    PubMed  Google Scholar 

  7. Marcantoni C, Ma LJ, Federspiel C, Fogo AB (2002) Hypertensive nephrosclerosis in African American versus Caucasians. Kidney Int 62:172–180

    Article  PubMed  Google Scholar 

  8. Sheats N, Lin Y, Zhao W, Cheek DAE, Lackland DT, Egan BM (2005) Prevalence, treatment, and control of hypertension among African American and Caucasians at primary care sites for medically under-served patients. Ethn Dis 15:25–32

    PubMed  Google Scholar 

  9. Bersamin A, Stafford RS, Winkleby MA (2009) Predictors of hypertension awareness, treatment, and control among Mexican American women and men. J Gen Intern Med 24(S3):521–527

    Article  PubMed  Google Scholar 

  10. Hirth RA (2007) The organization and financing of kidney dialysis and transplant care in the United States of America. Int J Health Care Finance Econ 7(4):301–318

    Article  PubMed  Google Scholar 

  11. http://www.usrds.org/atlas.htm. Accessed 1 June 2010

  12. Meyrier A, Simon P (1996) Nephroangiosclerosis and hypertension: things are not as simple as you might think. Nephrol Dial Transplant 11:2116–2120

    PubMed  CAS  Google Scholar 

  13. Xue JL, Eggers PW, Agodoa LY, Foley RN, Collins AJ (2007) Longitudinal study of racial and ethnic differences in developing end-stage renal disease among aged medicare beneficiaries. J Am Soc Nephrol 18:1299–1306

    Article  PubMed  Google Scholar 

  14. United States Renal Data System (1999) 1999 Annual report. Am J Kidney Dis 34(2 suppl 1):S1–S176

    Google Scholar 

  15. Schelling JR, Zarif L, Sehgal A, Iyengar S, Sedor JR(1999) Genetic susceptibility to end-stage renal disease. Curr Opin Nephrol Hypertens 8:465–472, and references cited therein

    Google Scholar 

  16. Yang J, Kamide K, Kokubo Y, Takiuchi S, Horio T, Matayoshi T, Yasuda H, Miwa Y, Yoshii M, Yoshihara F, Nakamura S, Nakahama H, Tomoike H, Miyata T, Kawano Y (2008) Associations of hypertension and its complications with variations in the xanthine dehydrogenase gene. Hypertens Res 31(5):931–940

    Article  PubMed  CAS  Google Scholar 

  17. Salem RM, Cadman PE, Chen Y, Rao F, Wen G, Hamilton BA, Rana BK, Smith DW, Stridsberg M, Ward HJ, Mahata SK, Bowden DW, Hicks PJ, Freedman BI, Schork NJ, O’Connor DT (2008) Chromogranin A polymorphisms are associated with hypertensive renal disease. J Am Soc Nephrol 19:600–614

    Article  PubMed  CAS  Google Scholar 

  18. Buraczynska M, Ksiazek P, Drop A, Zaluska W, Spasiewicz D, Ksiazek A (2006) Genetic polymorphisms of the rennin-angiotensin system in end-stage renal disease. Nephrol Dial Transplant 21:979–983

    Article  PubMed  CAS  Google Scholar 

  19. Fabris B, Borto M, Candido R, Barbone F, Cattin MR, Calci M, Scanferla F, Tizzoni L, Giacca M, Carretta R (2005) Genetic polymorphisms of the rennin-angiotensin-aldosterone system and renal insufficiency in essential hypertension. J Hypertens 23(2):309–316

    Article  PubMed  CAS  Google Scholar 

  20. Freedman BI, Hicks PJ, Bostrom MA, Cunningham ME, Liu Y, Divers J, Kopp JB, Winkler CA, Nelson GW, Langefeld CD, Bowden DW (2009) Polymorphisms in the non-muscle MYH9 are strongly associated with ESRD historically attributed to hypertension in African Americans. Kidney Int 75(7):736–745

    Article  PubMed  CAS  Google Scholar 

  21. Jozwiak L, Drop A, Buraczynska K, Ksiazek P, Mierzicki P, Buraczynska M (2004) Association of the human bradykinin B2 receptor gene with chronic renal failure. Mol Diagn 8(3):157–161

    Article  PubMed  Google Scholar 

  22. Rajnoch J, Viklicky O (2005) Angiogenesis and organ transplantation. Folia Microbiol 49(5):499–505

    Article  Google Scholar 

  23. Munis JJ, Toledo CI, Metzger IF, Sandrim VC, Tanus-Santos JE (2009) Interethnic differences in the distribution of clinically relevant vascular endothelial growth factor genetic polymorphisms. DNA Cell Biol 28(11):567–572

    Article  Google Scholar 

  24. Gonzalez JR, Armengol L, Sole X, Guino E, Mercader JM, Estivill X, Moreno V (2007) SNPassoc: an R package to perform whole genome association studies. Bioinformatics 23:654–655

    Article  CAS  Google Scholar 

  25. Lake SL, Lyon H, Tantisira K, Silverman EK, Weiss ST, Laird NM, Schaid DJ (2003) Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum Hered 55:56–65

    Article  PubMed  CAS  Google Scholar 

  26. Schrijvers BF, Flyvbjerg A, De Vriese AS (2004) The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 65:2003–2017

    Article  PubMed  CAS  Google Scholar 

  27. Facemire CS, Nixon AB, Griffiths R, Hurwitz H, Coffman TM (2009) VEGF receptor 2 controls blood pressure by regulating NO synthase expression. Hypertension 54:652–658

    Article  PubMed  CAS  Google Scholar 

  28. Rudnicki M, Perco P, Enrich J, Eder S, Heininger D, Bernthaler A, Wiesinger M, Sarkozi R, Noppert SJ, Schramek H, Mayer B, Oberbauer R, Mayer G (2009) Hypoxia response and VEGF-A expression in human proximal tubular epithelial cells in stable and progressive renal disease. Lab Invest 89:337–346

    Article  PubMed  CAS  Google Scholar 

  29. Advani A, Kelly D, Advani SL, Cox AJ, Thai K, Zhang Y, White KE, Gow RM, Marshall SM, Steer BM, Marsden PA, Rakoczy PE, Gilbert RE (2007) Role of VEGF in maintaining renal structure and function under normotensive and hypertensive conditions. Proc Natl Acad Sci 104(36):14448–14453

    Article  PubMed  CAS  Google Scholar 

  30. Ostendorf T, Kunter U, Eitner F, Loos A, Regele H, Kerjaschki D, Henninger DD, Janjic N, Floege J (1999) VEGF mediate glomerular endothelial repair. J Clin Invest 104:913–923

    Article  PubMed  CAS  Google Scholar 

  31. Khakoo AY, Sidman RL, Pasqualini R, Arap W (2008) Does the rennin-angiotensin system participate in regulation of human vasculogenesis and angiogenesis? Cancer Res 68(22):9112–9115, and references cited therein

    Google Scholar 

  32. Ayerder EF, Haksun E, Ulver DB, Koc E, Erten Y, Reis AK, Turgay A, Sindel S (2008) The relationship between vascular endothelial growth factor and microalbuminuria in patients with essential hypertension. Inter Med 47:1511–1516

    Article  Google Scholar 

  33. Shahbazi M, Fryer AA, Pravica V, Brogan IJ, Ramsay HM, Hutchinson IV, Harden PN (2002) Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. J Am Soc Nephrol 13:260–264

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study has been supported in part by the Mendez National Institute of Transplantation, Los Angeles, California; the College of Pharmacy, Western University of Health Sciences, Pomona, California, the California Korean-American Pharmacists Association, Los Angeles, California; and by the University of Kansas, Lawrence, Kansas.

Conflict of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author information

Authors and Affiliations

  1. University of Kansas, Lawrence, KS, USA

    Jae Wook Yang & Jianwen Fang

  2. University of Southern California, Los Angeles, CA, USA

    Ian V. Hutchinson & Tariq Shah

  3. Mendez National Institute of Transplantation, Los Angeles, CA, USA

    Ian V. Hutchinson, Tariq Shah & David I. Min

  4. St. Vincent Medical Center, Los Angeles, CA, USA

    Tariq Shah & David I. Min

  5. Western University of Health Sciences, 309 E. 2nd Street, Pomona, CA, 91766, USA

    David I. Min

Authors
  1. Jae Wook Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ian V. Hutchinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tariq Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianwen Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David I. Min
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David I. Min.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, J.W., Hutchinson, I.V., Shah, T. et al. Gene polymorphism of vascular endothelial growth factor −1154 G>A is associated with hypertensive nephropathy in a Hispanic population. Mol Biol Rep 38, 2417–2425 (2011). https://doi.org/10.1007/s11033-010-0376-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0376-8

Keywords

Search

Navigation