Skip to main content
Log in

T allele for VEGF-460 Gene Polymorphism at 5′-Untranslated Region is Associated with Higher Susceptibility of Leiomyoma

  • Note
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis and a mediator of sex steroid-induced cell growth and differentiation. We aimed to investigate if VEGF gene 5′-UTR −460 polymorphism could be used as markers of susceptibility in leiomyoma. Women were divided into two groups: (1) leiomyoma (n=159); (2) nonleiomyoma groups (n=131). VEGF gene −460 polymorphism were detected by polymerase chain reaction and BstUI restriction enzyme analysis. Genotypes and allelic frequencies between both groups were compared. We noted that the proportions of different VEGF polymorphisms in both groups were significantly different. Proportions of cuttable (C) homozygote/heterozygote/uncuttable (T) homozygote for VEGF in both groups were: (1) 0/32/68% and (2) 0/63/37%. Higher percentage of T homozygote and T allele presented in the leiomyoma population. Proportions of C/T alleles in both groups were: (1) 16/84% and (2) 32/68%. We concluded that T homozygotes and T allele of VEGF gene −460 polymorphism are associated with higher risk of leiomyoma development. Heterozygotes and C allele are related with lower risk of leiomyoma formation. VEGF gene polymorphism likely contributes to the pathogenesis of leiomyoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adams J, Carder PJ, Downey S, Forbes MA, MacLennan K, Allgar V, Kaufman S, Hallam S, Bicknell R, Walker JJ, Cairnduff F, Selby PJ, Perren TJ, Lansdown M, Banks RE (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 60:2898–2905

    PubMed  CAS  Google Scholar 

  • Akagi K, Ikeda Y, Miyazaki M, Abe T, Kinoshita J, Maehara Y, Sugimachi K (2000) Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues. Br J Cancer 83:887–891

    Article  PubMed  CAS  Google Scholar 

  • Ali AF, Fateen B, Ezzet A, Badawy H, Ramadan A, El-tobge A (2000) Elevated level of basic fibroblast growth factor in leiomyoma-related abnormal uterine bleeding and its reversal by interferon-alpha. Obstet Gynecol 95(4 Suppl 1):S6

    Article  Google Scholar 

  • Boehm KD, Daimon M, Gorodeski IG, Sheean LA, Utian WH, Ilan J (1990) Expression of the insulin-like and platelet-derived growth factor genes in human uterine tissues. Mol Reprod Dev 27:93–101

    Article  PubMed  CAS  Google Scholar 

  • Bragado R, Bello E, Requena L, Renedo G, Texeiro E, Alvarez MV, Castilla MA, Caramelo C (1999) Increased expression of vascular endothelial growth factor in pyogenic granulomas. Acta Derm Venereol 79:422–425

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Cheng D, Wu Q (1998) Changes of the gene expression of vascular endothelial growth factor in the lung of rats with chronic hypoxic pulmonary hypertension. Hua Xi Yi Ke Da Xue Xue Bao 29:233–236

    PubMed  CAS  Google Scholar 

  • Cramer DW (1992) Epidemiology of myomas. Semin Reprod Endocrinol 10:320–324

    Article  Google Scholar 

  • Ferrara N (1999) Molecular and biological properties of vascular endothelial growth factor. J Mol Med 77:527–543

    Article  PubMed  CAS  Google Scholar 

  • Ferrara N (2000) VEGF: an update on biological and therapeutic aspects. Curr Opin Biotechnol 11:617–624

    Article  PubMed  CAS  Google Scholar 

  • Ferriani RA, Charnock-Jones DS, Prentice A, Thomas EJ, Smith SK (1993) Immunohistochemical localization of acidic and basic fibroblast growth factors in normal human endometrium and endometriosis and the detection of their mRNA by polymerase chain reaction. Hum Reprod 8:11–16

    PubMed  CAS  Google Scholar 

  • Hamamichi Y, Ichida F, Yu X, Hirono KI, Uese KI, Hashimoto I, Tsubata S, Yoshida T, Futatani T, Kanegane H, Miyawaki T (2001) Neutrophils and mononuclear cells express vascular endothelial growth factor in acute Kawasaki disease: its possible role in progression of coronary artery lesions. Pediatr Res 49:74–80

    Article  PubMed  CAS  Google Scholar 

  • Holt RC, Ralph SA, Webb NJ, Watson CJ, Clark AG, Mathieson PW, Brenchley PE (2003) Steroid-sensitive nephrotic syndrome and vascular endothelial growth factor gene polymorphisms. Eur J Immunogenet 30:1–3

    Article  PubMed  CAS  Google Scholar 

  • Huminiecki L, Chan HY, Lui S, Poulsom R, Stamp G, Harris AL, Bicknell R (2001) Vascular endothelial growth factor transgenic mice exhibit reduced male fertility and placental rejection. Mol Hum Reprod 7:495

    Article  CAS  Google Scholar 

  • Hyder SM, Huang JC, Nawaz Z, Boettger-Tong H, Makela S, Chiappetta C, Stancel GM (2000a) Regulation of vascular endothelial growth factor expression by estrogens and progestins. Environ Health Perspect 108:785–790

    Article  PubMed  CAS  Google Scholar 

  • Hyder SM, Nawaz Z, Chiappetta C, Stancel GM (2000b) Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Cancer Res 60:3183–3190

    PubMed  CAS  Google Scholar 

  • Maeda T, Matsumura S, Hiranuma H, Jikko A, Furukawa S, Ishida T, Fuchihata H (1998) Expression of vascular endothelial growth factor in human oral squamous cell carcinoma: its association with tumour progression and p53 gene status. J Clin Pathol 51:771–775

    PubMed  CAS  Google Scholar 

  • Maloney J, Wang D, Duncan T, Voelkel N, Ruoss S (2000) Plasma vascular endothelial growth factor in acute mountain sickness. Chest 118:47–52

    Article  PubMed  CAS  Google Scholar 

  • Meliconi R, Pulsatelli L, Dolzani P, Boiardi L, Macchioni P, Salvarani C, Silvestri T, Frizziero L, Facchini A (2000) Vascular endothelial growth factor production in polymyalgia rheumatica. Arthritis Rheum 43:2472–2480

    Article  PubMed  CAS  Google Scholar 

  • Oehring RD, Miletic M, Valter MM, Pietsch T, Neumann J, Fimmers R, Schlegel U (1999) Vascular endothelial growth factor (VEGF) in astrocytic gliomas—a prognostic factor?. J Neurooncol 45:117–125

    Article  PubMed  CAS  Google Scholar 

  • Postlethwaite RJ, Brenchley PE (1999) Circulating vascular endothelial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome. Kidney Int 55:1063–1071

    Article  PubMed  Google Scholar 

  • Stoner M, Wang F, Wormke M, Nguyen T, Samudio I, Vyhlidal C, Marme D, Finkenzeller G, Safe S (2000) Inhibition of vascular endothelial growth factor expression in HEC1A endometrial cancer cells through interactions of estrogen receptor alpha and Sp3 proteins. J Biol Chem 275:22769–22779

    Article  PubMed  CAS  Google Scholar 

  • Strawn EY Jr, Novy MJ, Burry KA, Bethea CL (1995) Insulin-like growth factor I promotes leiomyoma cell growth in vitro. Am J Obstet Gynecol 172:1837–1844

    Article  PubMed  CAS  Google Scholar 

  • Tommola P, Pekonen F, Rutanen EM (1989) Binding of epidermal growth factor and insulin-like growth factor I in human myometrium and leiomyomata. Obstet Gynecol 74:658–662

    PubMed  CAS  Google Scholar 

  • Townsend DE, Sparkes RS, Baluda MC, McClelland G (1970) Unicellular histogenesis of uterine leiomyomas as determined by electrophoresis by glucose-6-phosphate dehydrogenase. Am J Obstet Gynecol 107:1168–1173

    PubMed  CAS  Google Scholar 

  • Uchida S, Shimada Y, Watanabe G, Tanaka H, Shibagaki I, Miyahara T, Ishigami S, Imamura M (1998) In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis. Br J Cancer 77:1704–1709

    PubMed  CAS  Google Scholar 

  • Viac J, Pernet I, Schmitt D, Claudy A (1999) Overexpression of circulating vascular endothelial growth factor (VEGF) in leukocytoclastic vasculitis. Arch Dermatol Res 291:622–623

    Article  PubMed  CAS  Google Scholar 

  • Wang G, Yang Z, Shou C (1997) The effect of antibody against vascular endothelial growth factor (VEGF) on tumor metastasis. Zhonghua Zhong Liu Za Zhi 19:407–409

    PubMed  CAS  Google Scholar 

  • Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12:1232–1235

    Article  PubMed  CAS  Google Scholar 

  • Zheng S, Wu Z, Ruan Y, Tang J (1998) Expression of vascular endothelial growth factor in hepatocellular carcinoma and its relationship to tumor growth and metastasis. J Tongji Med Univ 18:10–12

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fuu-Jen Tsai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hsieh, YY., Chang, CC., Tsai, FJ. et al. T allele for VEGF-460 Gene Polymorphism at 5′-Untranslated Region is Associated with Higher Susceptibility of Leiomyoma. Biochem Genet 46, 356–361 (2008). https://doi.org/10.1007/s10528-008-9150-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-008-9150-1

Keywords

Navigation