J Korean Med Sci.  2008 Feb;23(1):89-93. 10.3346/jkms.2008.23.1.89.

Interleukin-10 and Tumor Necrosis Factor-alpha Polymorphisms in Vascular Access Failure in Patients on Hemodialysis: Preliminary Data in Korea

  • 1Division of Nephrology, Eulji Hospital, Seoul, Korea.
  • 2Department of Internal Medicine, Korea University Hospital, Seoul, Korea. wonyong@korea.ac.kr


Neointimal hyperplasia causes vascular stenosis and subsequent thrombosis, which result in vascular access failure in patients undergoing hemodialysis. Interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-alpha) are involved in this inflammatory process. The aim of this study was to investigate the relationship between vascular access failure and various inflammatory markers including the genetic polymorphisms of IL-10 and TNF-alpha. Seventy-five patients on hemodialysis with an arteriovenous fistula in place or an artificial graft (18 with vascular access failure and 82 without failure) and 98 healthy individuals were genotyped for IL-10 and TNF-alpha single nucleotide polymorphisms. Clinical and laboratory data including serum IL-10 and TNF-alpha levels were compared. Stimulated IL-10 levels, from in vitro incubation of blood with lipopolysaccharide, were also obtained and compared. Female gender, hypoproteinemia, and hypertriglyceridemia were associated with vascular access failure. The basal TNF-alpha level was significantly higher in patients with access failure. The distribution of IL-10 and TNF-alpha genotype did not differ among patients with or without access failure. This study could not demonstrate a relationship between genetic polymorphisms and vascular access failure. However, an altered immune response and inflammation might contribute to vascular access failure.


Polymorphism, Single Nucleotide; Arteriovenous Shunt, Surgical; Constriction, Pathologic; Renal Dialysis

MeSH Terms

Arteriovenous Shunt, Surgical/*adverse effects
Catheters, Indwelling/*adverse effects
Cross-Sectional Studies
Middle Aged
*Polymorphism, Single Nucleotide
*Renal Dialysis
Tumor Necrosis Factor-alpha/blood/*genetics


  • Fig. 1 Comparison between percentage frequencies of interleukin-10 and tumour necrosis factor-α genotypes in healthy controls, good functioning access groups and access failure group.

  • Fig. 2 Comparison between interleukin-10 single nucleotide polymorphisms in in vitro production of interleukin-10 protein in peripheral blood mononuclear cells after stimulating with lipopolysaccharide.

  • Fig. 3 Comparison of the serum tumour necrosis factor-α level between the good functioning access group and the access failure group.


1. Rekhter M, Nicholls S, Ferguson M, Gordon D. Cell proliferation in human arteriovenous fistulas used for hemodialysis. Arterioscler Thromb. 1993. 13:609–617.
2. Roy-Chaudhury P, Kelly BS, Miller MA, Reaves A, Armstrong J, Nanayakkara N, Heffelfinger SC. Venous neointimal hyperplasia in polytetrafluoroethylene dialysis grafts. Kidney Int. 2001. 59:2325–2334.
3. Ram S, Bass K, Abreo K, Baier RJ, Kruger TE. Tumor necrosis factor-alpha -308 gene polymorphism is associated with synthetic hemodialysis graft failure. J Investig Med. 2003. 51:19–26.
4. Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, Tsunoda T, Sato H, Hori M, Nakamura Y, Tanaka T. Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat Genet. 2002. 32:650–654.
5. Heine GH, Ulrich C, Sester U, Sester M, Kohler H, Girndt M. Transforming growth factor beta1 genotype polymorphisms determine AV fistula patency in hemodialysis patients. Kidney Int. 2003. 64:1101–1107.
6. Lemson MS, Tordoir JH, Daemen MJ, Kitslaar PJ. Intimal hyperplasia in vascular grafts. Eur J Vasc Endovasc Surg. 2000. 19:336–350.
7. Rus HG, Niculescu F, Vlaicu R. Tumor necrosis factor-alpha in human arterial wall with atherosclerosis. Atherosclerosis. 1991. 89:247–254.
8. Clausell N, Molossi S, Sett S, Rabinovitch M. In vivo blockade of tumor necrosis factor-alpha in cholesterol-fed rabbits after cardiac transplant inhibits acute coronary artery neointimal formation. Circulation. 1994. 89:2768–2779.
9. Feldman LJ, Aguirre L, Ziol M, Bridou JP, Nevo N, Michel JB, Steg PG. Interleukin-10 inhibits intimal hyperplasia after angioplasty or stent implantation in hypercholesterolemic rabbits. Circulation. 2000. 101:908–916.
10. Rees LE, Wood NA, Gillespie KM, Lai KN, Gaston K, Mathieson PW. The interleukin-10-1082 G/A polymorphism: allele frequency in different populations and functional significance. Cell Mol Life Sci. 2002. 59:560–569.
11. Rosenwasser LJ, Borish L. Genetics of atopy and asthma: the rationale behind promoter-based candidate gene studies (IL-4 and IL-10). Am J Respir Crit Care Med. 1997. 156:S152–S155.
12. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997. 94:3195–3199.
13. Haukim N, Bidwell JL, Smith AJ, Keen LJ, Gallagher G, Kimberly R, Huizinga T, McDermott MF, Oksenberg J, McNicholl J, Pociot F, Hardt C, D'Alfonso S. Cytokine gene polymorphism in human disease: on-line databases, supplement 2. Genes Immun. 2002. 3:313–330.
14. Koch W, Tiroch K, von Beckerath N, Schomig A, Kastrati A. Tumor necrosis factor-alpha, lymphotoxin-alpha, and interleukin-10 gene polymorphisms and restenosis after coronary artery stenting. Cytokine. 2003. 24:161–171.
15. Pawlik A, Kurzawski M, Szklarz BG, Herczynska M, Drozdzik M. Interleukin-10 promoter polymorphism in patients with rheumatoid arthritis. Clin Rheumatol. 2005. 24:480–484.
16. Abbott WG, Rigopoulou E, Haigh P, Cooksley H, Mullerova I, Novelli M, Winstanley A, Williams R, Naoumov NV. Single nucleotide polymorphisms in the interferon-gamma and interleukin-10 genes do not influence chronic hepatitis C severity or T-cell reactivity to hepatitis C virus. Liver Int. 2004. 24:90–97.
17. Zoodsma M, Nolte IM, Schipper M, Oosterom E, van der Steege G, de Vries EG, Te Meerman GJ, van der Zee AG. Interleukin-10 and Fas polymorphisms and susceptibility for (pre) neoplastic cervical disease. Int J Gynecol Cancer. 2005. 15:Suppl 3. 282–290.
18. Berglund M, Thunberg U, Roos G, Rosenquist R, Enblad G. The interleukin-10 gene promoter polymorphism (-1082) does not correlate with clinical outcome in diffuse large B-cell lymphoma. Blood. 2005. 105:4894–4895.
19. Wu JM, Bensen-Kennedy D, Miura Y, Thoburn CJ, Armstrong D, Vogelsang GB, Hess AD. The effects of interleukin 10 and interferon gamma cytokine gene polymorphisms on survival after autologous bone marrow transplantation for patients with breast cancer. Biol Blood Marrow Transplant. 2005. 11:455–464.
20. Reynard MP, Turner D, Navarrete CV. Allele frequencies of polymorphisms of the tumour necrosis factor-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK. Eur J Immunogenet. 2000. 27:241–249.
21. Ernandez T, Saudan P, Berney T, Merminod T, Bednarkiewicz M, Martin PY. Risk Factors for Early Failure of Native Arteriovenous Fistulas. Nephron Clin Pract. 2005. 101:c39–c44.
22. De Marchi S, Falleti E, Giacomello R, Stel G, Cecchin E, Sepiacci G, Bortolotti N, Zanello F, Gonano F, Bartoli E. Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. J Am Soc Nephrol. 1996. 7:1169–1177.
Full Text Links
  • JKMS
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr