Genes & Genomics

, Volume 37, Issue 6, pp 551–558 | Cite as

Gender-specific association of polymorphisms in the 5′-UTR and 3′-UTR of VEGF gene with hypertensive patients

Research Article

Abstract

Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors. VEGF plasma levels have been reported to be significantly elevated in the patients with hypertension. This study aims to elucidate the associations of the VEGF −634G>C and 936C>T polymorphisms with the hypertensive patients in Korea. Genotyping of the VEGF polymorphisms was carried out by polymerase chain reaction and endonuclease digestion. The C allele of the VEGF634G>C polymorphism and T allele of the 936C>T polymorphism were significantly higher in the hypertensive patients than in the normotensive controls. When the data of the genotype were stratified by gender, the association was gender-specific. We also found the associations of the haplotypes, composed of the VEGF634G>C and 936C>T polymorphisms, with hypertensive group. Dominant models of 634G>C and 936C>T polymorphisms were associated with risk components of hypertension, according to the stratification analysis. Thus, this study demonstrates that the VEGF −634G>C and 936C>T polymorphisms may provide important genetic markers in identifying people at risk for hypertension. So far, association studies of VEGF gene polymorphisms with the hypertensive patients were rare. Therefore, further evaluation is required in other ethnic or racial populations with large samples to confirm our data.

Keywords

Association Gender-specific Haplotype Hypertension VEGF polymorphism 

References

  1. Adams J, Carder PJ, Downey S, Forbes MA, MacLennan K, Allgar V, Kaufman S, Hallam S, Bicknell R, Walker JJ et al (2000) Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. Cancer Res 60:2898–2905PubMedGoogle Scholar
  2. Akhter Q, Masood A, Ashraf R, Majid S, Rasool S, Khan T, Rashid T, Sameer AS, Ganai BA (2012) Polymorphisms in the 3′UTR of the human leptin gene and their role in hypertension. Mol Med Rep 5:1058–1062PubMedCentralPubMedGoogle Scholar
  3. Bae SJ, Kim JW, Kang H, Hwang SG, Oh D, Kim NK (2008) Gender-specific association between polymorphism of vascular endothelial growth factor (VEGF 936 C>T) gene and colon cancer in Korea. Anticancer Res 28:1271–1276PubMedGoogle Scholar
  4. Chen CY, Shyu AB (1995) AU-rich elements: characterization and importantance in mRNA degradation. TIBS 20:465–470PubMedGoogle Scholar
  5. Gargett CE, Lederman F, Heryanto B, Gambino LS, Rogers PA (2001) Focal vascular endothelial growth factor correlates with angiogenesis in human endometrium. Role of intravascular neutrophils. Hum Reprod 16:1065–1075CrossRefPubMedGoogle Scholar
  6. Hamedian AA, Esteghamati A, Noshad S, Mozafari M, Moin-Tavakkoli H, Nakhjavani M, Mahmoudi T, Nikzamir M, Safary R, Nikzamir A (2012) Vascular endothelial growth factor (VEGF) +405 C/G polymorphism is associated with essential hypertension in a population from Tehran of Iran. Mol Biol Rep 39:6213–6218CrossRefPubMedGoogle Scholar
  7. Kato N (2002) Genetic analysis in human hypertension. Hypertens Res 25:319–327CrossRefPubMedGoogle Scholar
  8. Kern JA, Warnock LJ, McCafferty JD (1997) The 3′ untranslated region of IL-1beta regulates protein production. J Immunol 158:1187–1193PubMedGoogle Scholar
  9. Kim OJ, Hong SH, Oh SH, Kim TG, Min KT, Oh D, Kim NK (2011) Association between VEGF polymorphisms and homocysteine levels in patients with ischemic stroke and silent brain infarction. Stroke 42:2393–2402CrossRefPubMedGoogle Scholar
  10. Kim YR, Kim SH, Kang SH, Kim HJ, Kong MH, Hong S (2014) Association of the K173R variant and haplotypes in the aldosterone synthase gene with essential hypertension. Genes Genom 35:13–20Google Scholar
  11. Koukourakis MI, Papazoglou D, Giatromanolaki A, Bougioukas G, Maltezos E, Sivridis E (2014) VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer. Lung Cancer 46:293–298CrossRefGoogle Scholar
  12. Kwon YK, Hecht NB (1991) Cytoplasmic protein binding to highly conserved sequences in the 3′untranslated region of mouse protamine 2 mRNA, a translationally regulated transcript of male germ cells. Proc Natl Acad Sci USA 88:3584–3588PubMedCentralCrossRefPubMedGoogle Scholar
  13. Lacchini R, Luizon MR, Gasparini S, Ferreira-Sae MC, Schreiber R, Nadruz W Jr, Tanus-Santos JE (2014) Effect of genetic polymorphisms of vascular endothelial growth factor on left ventricular hypertrophy in patients with systemic hypertension. Am J Cardiol 113:491–496CrossRefPubMedGoogle Scholar
  14. Lambrechts D, Poesen K, Fernández-Santiago R, Al-Chalabi A, Del Bo R, Van Vught PW, Khan S, Marklund SL, Brockington A, van Marion I et al (2009) Meta-analysis of vascular endothelial growth factor variations in amyotrophic lateral sclerosis: increased susceptibility in male carriers of the -2578AA genotype. J Med Genet 46:840–846CrossRefPubMedGoogle Scholar
  15. Minchenko A, Bauer T, Salceda S, Caro J (1994) Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo. Lab Invest 71:374–379PubMedGoogle Scholar
  16. Palmirotta R, Ferroni P, Ludovici G, Martini F, Savonarola A, D’Alessandro R, Raparelli V, Proietti M, Scarno A, Riondino S et al (2010) VEGF-A gene promoter polymorphisms and microvascular complications in patients with essential hypertension. Clin Biochem 43:1090–1095CrossRefPubMedGoogle Scholar
  17. Petrovic D (2010) The role of vascular endothelial growth factor gene as the genetic marker of atherothrombotic disorders and in the gene therapy of coronary artery disease. Cardiovasc Hematol Agents Med Chem 8:47–54CrossRefPubMedGoogle Scholar
  18. Prasad MK, Bhalla K, Pan ZH, O’Connell JR, Weder AB, Chakravarti A, Tian B, Chang YP (2013) A polymorphic 3′UTR element in ATP1B1 regulates alternative polyadenylation and is associated with blood pressure. PLoS ONE 8:e76290PubMedCentralCrossRefPubMedGoogle Scholar
  19. Renner W, Pilger E (1999) Simultaneous in vitro quantitation factors of vascular endothelial growth factor mRNA splice variants. J Vasc Res 36:133–138CrossRefPubMedGoogle Scholar
  20. Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger EA (2000) Common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vasc Res 37:443–448CrossRefPubMedGoogle Scholar
  21. 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 13:260–264PubMedGoogle Scholar
  22. Siervo M, Ruggiero D, Sorice R, Nutile T, Aversano M, Stephan BC, Ciullo M (2010) Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome. J Intern Med 268:338–347CrossRefPubMedGoogle Scholar
  23. Siervo M, Ruggiero D, Sorice R, Nutile T, Aversano M, Iafusco M, Vetrano F, Wells JC, Stephan BC, Ciullo M (2012) Body mass index is directly associated with biomarkers of angiogenesis and inflammation in children and adolescents. Nutrition 28:262–266CrossRefPubMedGoogle Scholar
  24. Steffensen KD, Waldstrøm M, Brandslund I, Jakobsen A (2010) The relationship of VEGF polymorphisms with serum VEGF levels and progression-free survival in patients with epithelial ovarian cancer. Gynecol Oncol 117:109–116CrossRefPubMedGoogle Scholar
  25. Stevens A, Soden J, Brenchley PE, Ralph S, Ray DW (2003) Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter. Cancer Res 63:812–816PubMedGoogle Scholar
  26. Stumpf C, Jukic J, Yilmaz A, Raaz D, Schmieder RE, Daniel WG, Garlichs CD (2009) Elevated VEGF-plasma levels in young patients with mild essential hypertension. Eur J Clin Invest 39:31–36CrossRefPubMedGoogle Scholar
  27. Tanira MO, Al Balushi KA (2005) Genetic variations related to hypertension: a review. J Hum Hypertens 19:7–19CrossRefPubMedGoogle Scholar
  28. Watson CJ, Webb NJA, Bottomley MJ, Brenchley PEC (2000) Identification of polymorphisms within the vascular endothelial growth factor gene: correlation with variation in VEGF protein production. Cytokine 12:1232–1235CrossRefPubMedGoogle Scholar
  29. Yang Z, Venardos K, Jones E, Morris BJ, Chin-Dusting J, Kaye DM (2007) Identification of a novel polymorphism in the 3′UTR of the l-arginine transporter gene SLC7A1: contribution to hypertension and endothelial dysfunction. Circulation 115:1269–1274PubMedGoogle Scholar
  30. Yang JW, Hutchinson IV, Shah T, Fang J, Min DI (2011) Gene polymorphism of vascular endothelial growth factor −1154 G>A is associated with hypertensive nephropathy in a Hispanic population. Mol Biol Rep 38:2417–2425CrossRefPubMedGoogle Scholar

Copyright information

© The Genetics Society of Korea and Springer-Science and Media 2015

Authors and Affiliations

  1. 1.Department of Laboratory Medicine, School of MedicineJeju National UniversityJejuRepublic of Korea
  2. 2.Department of Science Education, Teachers CollegeJeju National UniversityJejuRepublic of Korea

Personalised recommendations