The Korean journal of internal medicine

  • 제27권3호
  • /
  • Pages.327-337
  • /
  • 2012
  • /
  • 1226-3303(pISSN)
  • /
  • 2005-6648(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
권호 표지
DOI QR코드

DOI QR Code

Interleukin-6 -634 C/G and -174 G/C Polymorphisms in Korean Patients Undergoing Hemodialysis

  • Ryu, Jung-Hwa (Division of Nephrology, Department of Internal Medicine, Ewha Womans University School of Medicine) ;
  • Kim, Seung-Jung (Division of Nephrology, Department of Internal Medicine, Ewha Womans University School of Medicine)
  • 발행 : 2012.09.01
⟨ 이전 논문 다음 논문 ⟩

초록

Background/Aims: Chronic inflammatory status is a possible risk factor for vascular access dysfunction in hemodialysis (HD) patients, but susceptibility differences appear among individuals. Interleukin (IL)-6 is a well-known inflammatory cytokine with various polymorphisms. We examined whether IL-6 polymorphisms are associated with vascular access dysfunction in HD patients. Methods: A total of 80 HD patients (including 42 diabetic patients) were enrolled. Polymorphisms in the IL-6 gene promoter (-634 C/G and -174 G/C) were studied using restriction length polymorphism polymerase chain reaction analysis. Vascular access patency was compared between the patient groups with respect to IL-6 polymorphisms. An additional 89 healthy individuals were enrolled in the control group. Plasma IL-6 levels were de termined by enzyme-linked immunosorbent assay. Results: The GG genotype and G allele at position -634 in the IL-6 promoter were more frequently observed in HD patients than in controls. Furthermore, the distribution of the -634 polymorphism differed according to vascular access patency in non-diabetic HD patients. However, the G allele was not a significant risk factor for early access failure. No significant association appeared between the IL-6 -634 C/G polymorphism and plasma IL-6 levels. The C allele of the IL-6 -174 G/C polymorphism was not detected in our study population. Conclusions: The IL-6 -634 G allele appears with greater frequently in patients with end-stage renal disease and may be associated with vascular access dysfunction in non-diabetic HD patients.

키워드

참고문헌

  1. De Marchi S, Falleti E, Giacomello R, et al. Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. J Am Soc Nephrol 1996;7:1169-1177.
  2. Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648-658. https://doi.org/10.1046/j.1523-1755.1999.00273.x
  3. Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2000;35:469-476. https://doi.org/10.1016/S0272-6386(00)70200-9
  4. Kaysen GA. The microinflammatory state in uremia: causes and potential consequences. J Am Soc Nephrol 2001;12:1549-1557.
  5. Stenvinkel P, Pecoits-Filho R, Lindholm B; for the Dial-Gene Consortium. Gene polymorphism association studies in dialysis: the nutrition-inf lammation axis. Semin Dial 2005;18:322-330. https://doi.org/10.1111/j.1525-139X.2005.18317.x
  6. Yao Q, Lindholm B, Stenvinkel P. Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients. Hemodial Int 2004;8:118-129. https://doi.org/10.1111/j.1492-7535.2004.01085.x
  7. Rao M, Wong C, Kanetsky P, et al. Cytokine gene polymorphism and progression of renal and cardiovascular diseases. Kidney Int 2007;72:549-556. https://doi.org/10.1038/sj.ki.5002391
  8. Rao M, Guo D, Perianayagam MC, et al. Plasma interleukin-6 predicts cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2005;45:324-333. https://doi.org/10.1053/j.ajkd.2004.09.018
  9. Brull DJ, Montgomery HE, Sanders J, et al. Interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 2001;21:1458-1463. https://doi.org/10.1161/hq0901.094280
  10. Losito A, Kalidas K, Santoni S, Jeffery S. Association of interleukin-6 -174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients. Kidney Int 2003;64:616-622. https://doi.org/10.1046/j.1523-1755.2003.00119.x
  11. Pigott R, Dillon LP, Hemingway IH, Gearing AJ. Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun 1992;187:584-589. https://doi.org/10.1016/0006-291X(92)91234-H
  12. Ikeda U, Ikeda M, Oohara T, et al. Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner. Am J Physiol 1991;260(5 Pt 2):H1713-H1717.
  13. Juhan-Vague I, Alessi MC. Plasminogen activator inhibitor 1 and atherothrombosis. Thromb Haemost 1993;70:138-143.
  14. Fishman D, Faulds G, Jeffery R, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 1998;102:1369-1376. https://doi.org/10.1172/JCI2629
  15. Hulkkonen J, Pertovaara M, A ntonen J, Pasternack A, Hurme M. Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL-6 gene in primary Sjogren's syndrome and correlate with the clinical manifestations of the disease. Rheumatology (Oxford) 2001;40:656-661. https://doi.org/10.1093/rheumatology/40.6.656
  16. Aker S, Bantis C, Reis P, et al. Inf luence of interleukin-6 G-174C gene polymorphism on coronary artery disease, cardiovascular complications and mortality in dialysis patients. Nephrol Dial Transplant 2009;24:2847-2851. https://doi.org/10.1093/ndt/gfp141
  17. Kitamura A, Hasegawa G, Obayashi H, et al. Interleukin-6 polymorphism (-634 C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes. Diabet Med 2002;19:1000-1005. https://doi.org/10.1046/j.1464-5491.2002.00844.x
  18. Nakajima T, Ota N, Yoshida H, Watanabe S, Suzuki T, Emi M. Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women. Genes Immun 1999;1:115-119. https://doi.org/10.1038/sj.gene.6363642
  19. Buraczynska M, Jozwiak L, Ksiazek P, Borowicz E, Mierzicki P. Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis. Transl Res 2007;150:101-105. https://doi.org/10.1016/j.trsl.2007.03.003
  20. Chang CJ, Ko YS, Ko PJ, et al. Thrombosed arteriovenous fistula for hemodialysis access is characterized by a marked inflammatory activity. Kidney Int 2005;68:1312-1319. https://doi.org/10.1111/j.1523-1755.2005.00529.x
  21. Liu BC, Li L, Gao M, Wang YL, Yu JR. Microinflammation is involved in the dysfunction of arteriovenous fistula in patients with maintenance hemodialysis. Chin Med J (Engl) 2008;121:2157-2161.
  22. Marrone D, Pertosa G, Simone S, et al. Local activation of interleukin 6 signaling is associated with arteriovenous fistula stenosis in hemodialysis patients. Am J Kidney Dis 2007;49:664-673. https://doi.org/10.1053/j.ajkd.2007.02.266
  23. Zhai R, Liu G, Yang C, Huang C, Wu C, Christiani DC. The G to C polymorphism at -174 of the interleukin-6 gene is rare in a Southern Chinese population. Pharmacogenetics 2001;11:699-701. https://doi.org/10.1097/00008571-200111000-00008
  24. Zheng C, Huang DR, Bergenbrant S, et al. Interleukin 6, tumour necrosis factor alpha, interleukin 1beta and interleukin 1 receptor antagonist promoter or coding gene polymorphisms in multiple myeloma. Br J Haematol 2000;109:39-45. https://doi.org/10.1046/j.1365-2141.2000.01963.x
  25. Humphries SE, Luong LA, Ogg MS, Hawe E, Miller GJ. The interleukin-6 -174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 2001;22:2243-2252. https://doi.org/10.1053/euhj.2001.2678
  26. Cox ED, Hoffmann SC, DiMercurio BS, et al. Cytokine polymorphic analyses indicate ethnic differences in the allelic distribution of interleukin-2 and interleukin-6. Transplantation 2001;72:720-726. https://doi.org/10.1097/00007890-200108270-00027
  27. Lim CS, Zheng S, Kim YS, et al. The-174 G to C polymorphism of interleukin-6 gene is very rare in Koreans. Cytokine 2002;19:52-54. https://doi.org/10.1006/cyto.2002.1951
  28. Burzotta F, Iacoviello L, Di Castelnuovo A, et al. Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization. Am J Cardiol 2001;88:1125-1128. https://doi.org/10.1016/S0002-9149(01)02046-X
  29. Bennet AM, Prince JA, Fei GZ, et al. Interleukin-6 serum levels and genotypes influence the risk for myocardial infarction. Atherosclerosis 2003;171:359-367. https://doi.org/10.1016/j.atherosclerosis.2003.08.029
  30. Fernandez-Real JM, Broch M, Vendrell J, Richart C, Ricart W. Interleukin-6 gene polymorphism and lipid abnormalities in healthy subjects. J Clin Endocrinol Metab 2000;85:1334-1339. https://doi.org/10.1210/jc.85.3.1334
  31. Mittal RD, Manchanda PK. Association of interleukin (IL)-4 intron-3 and IL-6 -174 G/C gene polymorphism w ith susceptibility to end-stage renal disease. Immunogenetics 2007;59:159-165. https://doi.org/10.1007/s00251-006-0182-6
  32. Brull DJ, Leeson CP, Montgomery HE, et al. The effect of the Interleukin-6-174 G > C promoter gene polymorphism on endothelial function in healthy volunteers. Eur J Clin Invest 2002;32:153-157. https://doi.org/10.1046/j.1365-2362.2002.00966.x
  33. Stoica AL, Stoica E, Constantinescu I, Uscatescu V, Ginghina C. Interleukin-6 and interleukin-10 gene polymorphism, endothelial dysf unction, and postoperative prognosis in patients with peripheral arterial disease. J Vasc Surg 2010;52:103-109. https://doi.org/10.1016/j.jvs.2010.01.088
  34. Danielsson P, Truedsson L, Eriksson KF, Norgren L. Inflammatory markers and IL-6 polymorphism in peripheral arterial disease with and without diabetes mellitus. Vasc Med 2005;10:191-198. https://doi.org/10.1191/1358863x05vm617oa
  35. Libra M, Signorelli SS, Bevelacqua Y, et al. Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory markers in patients with type 2 diabetes and peripheral arterial disease. J Clin Pathol 2006;59:211-215. https://doi.org/10.1136/jcp.2004.025452
  36. Kiszel P, Mako V, Prohaszka Z, Cervenak L. Interleukin-6-174 promoter polymorphism does not influence IL-6 production after LPS and IL-1 beta stimulation in human umbilical cord vein endothelial cells. Cytokine 2007;40:17-22. https://doi.org/10.1016/j.cyto.2007.08.001

피인용 문헌

  1. Significant Impact of IL-6 -174G/C but Inverse Relation with -634 C/G Polymorphism in Patients with Non-Small Cell Lung Cancer in Kashmiri Population vol.44, pp.4, 2015, https://doi.org/10.3109/08820139.2015.1004336
  2. IL-6 and MCP-1 genetic polymorphisms are predictive of decreased platelet counts caused by chemoradiotherapy in esophageal cancer vol.13, pp.3, 2016, https://doi.org/10.1007/s10388-016-0522-z
  3. Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV vol.42, pp.4, 2020, https://doi.org/10.1590/2175-8239-jbn-2019-0188
  4. Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV vol.42, pp.4, 2020, https://doi.org/10.1590/2175-8239-jbn-2019-0188
  5. Interleukin 6 (rs1800795) and pentraxin 3 (rs2305619) polymorphisms-association with inflammation and all-cause mortality in end-stage-renal disease patients on dialysis vol.11, pp.1, 2012, https://doi.org/10.1038/s41598-021-94075-x
  6. Is there a correlation between -174(G/C) polymorphism of IL-6 gene and the incidence of acute myocardial infarction? vol.19, pp.1, 2012, https://doi.org/10.1186/s43141-021-00243-x