International Urology and Nephrology

, Volume 47, Issue 3, pp 551–556 | Cite as

The protective effect of MCP-1 -2518 A>G promoter polymorphism in Turkish chronic renal failure patients requiring long-term hemodialysis

  • Binnur Bagci
  • Gokhan Bagci
  • Ferhan Candan
  • Ozturk Ozdemir
  • Ilhan Sezgin
Nephrology - Original Paper

Abstract

Objective

Monocyte chemoattractant protein-1 (MCP-1) plays a major role in the pathogenesis and progression of different types of human renal disease. Therefore, in this study, we aimed to investigate the effect of MCP-1 gene -2518 A>G promoter polymorphism in chronic renal failure (CRF) patients requiring long-term hemodialysis.

Methods

The study population consisted of 201 adult CRF patients requiring long-term hemodialysis and 194 healthy controls. The polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique was used for genotyping of MCP-1 -2518 A>G polymorphism in the CRF patients and healthy controls.

Results

There were statistically significant differences in terms of genotypic (χ2 = 12.69, p = 0.02) and allelic (χ2 = 5.72, p = 0.02) frequencies of MCP-1 -2518 A>G between CRF patients and control subjects. According to our results, in the patient group MCP-1 -2518 AA genotype frequency was significantly higher than that of control group. On the other hand, heterozygous AG genotype frequency in the control group was significantly higher than that of the study group. Three different main disease subgroups of CRF (hypertension, diabetes mellitus, and atherosclerosis) patients were also evaluated, and significant associations were found between hypertension (genotype: χ2 = 9.28, p = 0.01; allele: χ2 = 6.00, p = 0.01), atherosclerosis (genotype: χ2 = 5.37, p = 0.02; allele: χ2 = 4.13, p = 0.04), and distributions of MCP-1 -2518 A>G genotypes and alleles. However, no significant association was found between diabetes mellitus and distributions of MCP-1 -2518 A>G genotype and allele frequencies (genotype: χ2 = 2.37, p = 0.3; allele: χ2 = 1.88, p = 0.17).

Conclusion

Current data show that MCP-1 -2518 AA genotype may cause susceptibility to CRF, while G allele may have a protective effect against development of CRF. In addition, MCP-1 -2518 AA genotype seems to associate with CRF originated from hypertension and atherosclerosis in our study population.

Keywords

MCP-1 Chronic renal failure Polymorphism Hypertension Diabetes mellitus Atherosclerosis 

References

  1. 1.
    Segerer S, Nelson PJ (2005) Chemokines in renal diseases. Sci World J 29:835–844CrossRefGoogle Scholar
  2. 2.
    Sean Eardley K, Cockwell P (2005) Macrophages and progressive tubulointerstitial disease. Kidney Int 68:437–455CrossRefPubMedGoogle Scholar
  3. 3.
    Wada T, Yokoyama H, Kobayashi K (2000) Chemokines: new target molecules in renal diseases. Clin Exp Nephrol 4:273–280CrossRefGoogle Scholar
  4. 4.
    Eis V, Vielhauer V, Anders HJ (2004) Targeting the chemokine network in renal inflammation. Arch Immunol Ther Exp (Warsz) 52:164–172Google Scholar
  5. 5.
    Segerer S, Nelson PJ, Schlöndorff D (2000) Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies. J Am Soc Nephrol 11:152–176PubMedGoogle Scholar
  6. 6.
    Furuichi K, Wada T, Kaneko S (2011) Cytokines and chemokines as therapeutic targets for ischemic kidney injury. Inflamm Regen 31:365–369CrossRefGoogle Scholar
  7. 7.
    Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 29:313–326CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Eardley KS, Zehnder D, Quinkler M, Lepenies J, Bates RL, Savage CO, Howie AJ, Adu D, Cockwell P (2006) The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease. Kidney Int 69:1189–1197CrossRefPubMedGoogle Scholar
  9. 9.
    Mori H, Kaneko Y, Narita I, Goto S, Saito N, Kondo D, Sato F, Ajiro J, Saga D, Ogawa A, Sakatsume M, Ueno M, Tabei K, Gejyo F (2005) Monocyte chemoattractant protein-1 A-2518G gene polymorphism and renal survival of Japanese patients with immunoglobulin A nephropathy. Clin Exp Nephrol 9:297–303CrossRefPubMedGoogle Scholar
  10. 10.
    Viedt C, Dechend R, Fei J, Hänsch GM, Kreuzer J, Orth SR (2002) MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-kB and activating protein-1. J Am Soc Nephrol 13:1534–1547CrossRefPubMedGoogle Scholar
  11. 11.
    Viedt C, Vogel J, Athanasiou T, Shen W, Orth SR, Kübler W, Kreuzer J (2002) Monocyte chemoattractant protein-1 induces proliferation and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-kB and activator protein-1. Arterioscler Thromb Vasc Biol 22:914–920CrossRefPubMedGoogle Scholar
  12. 12.
    Tesch GH, Maifert S, Schwarting A, Rollins BJ, Kelley VR (1999) Monocyte chemoattractant protein 1–dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Faslpr mice. J Exp Med 190:1813–1824CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Bird JE, Giancarli MR, Kurihara T, Kowala MC, Valentine MT, Gitlitz PH, Pandya DG, French MH, Durham SK (2000) Increased severity of glomerulonephritis in C-C chemokine receptor 2 knockout mice. Kidney Int 57:129–136CrossRefPubMedGoogle Scholar
  14. 14.
    Sezgin I, Koksal B, Bagci G, Kurtulgan HK, Ozdemir O (2011) CCR2 polymorphism in chronic renal failure patients requiring long-term hemodialysis. Intern Med 50:2457–2461CrossRefPubMedGoogle Scholar
  15. 15.
    Rovin BH, Lu L, Saxena R (1999) A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun 259:344–348CrossRefPubMedGoogle Scholar
  16. 16.
    Jibiki T, Terai M, Shima M, Ogawa A, Hamada H, Kanazawa M, Yamamoto S, Oana S, Kohno Y (2001) Monocyte chemoattractant protein-1 gene regulatory region polymorphism and serum levels of monocyte chemoattractant protein-1 in Japanese patients with Kawasaki disease. Arthritis Rheum 44:2211–2212CrossRefPubMedGoogle Scholar
  17. 17.
    Kim MJ, Tam FW (2011) Urinary monocyte chemoattractant protein-1 in renal disease. Clin Chim Acta 412:2022–2030CrossRefPubMedGoogle Scholar
  18. 18.
    Tesch GH, Schwarting A, Kinoshita K, Lan HY, Rollins BJ, Kelley VR (1999) Monocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis. J Clin Invest 103:73–80CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Ozdemir O, Kayatas M, Cetinkaya S, Yildirim ME, Silan F, Kurtulgan HK, Koksal B, Urfali M, Candan F (2014) Bcıı-RFLP profiles for serum amiloid A1 and mutated MEFV gene prevalence in chronic renal failure patients requiring long-term hemodialysis. Ren Fail. doi:10.3109/0886022X.2014.982954 Google Scholar
  20. 20.
    Sanders SK, Crean SM, Boxer PA, Kellner D, LaRosa GJ, Hunt SW (2000) Functional differences between monocyte chemotactic protein-1 receptor A and monocyte chemotactic protein-1 receptor B expressed in a Jurkat T cell. J Immunol 165:4877–4883CrossRefPubMedGoogle Scholar
  21. 21.
    Cho ML, Yoon BY, Ju JH, Jung YO, Jhun JY, Park MK, Cho CS, Kim HY (2007) Expression of CCR2A, an isoform of MCP-1 receptor, is increased by MCP-1, CD40 ligand and TGF-beta in fibroblast like synoviocytes of patients with RA. Exp Mol Med 39:499–507CrossRefPubMedGoogle Scholar
  22. 22.
    Steinmetz OM, Panzer U, Harendza S, Mertens PR, Ostendorf T, Floege J, Helmchen U, Stahl RA (2004) No association of the –2518 MCP-1 A/G promoter polymorphism with incidence and clinical course of IgA nephropathy. Nephrol Dial Transplant 19:596–601CrossRefPubMedGoogle Scholar
  23. 23.
    Malafronte P, Vieira JM Jr, Pereira AC, Krieger JE, Barros RT, Woronik V (2010) Association of the MCP-1 -2518 A/G polymorphism and no association of its receptor CCR2 -64 V/I polymorphism with lupus nephritis. J Rheumatol 37:776–782CrossRefPubMedGoogle Scholar
  24. 24.
    Buraczynska M, Skublewska AB, Buraczynska K, Ksiazek A (2008) Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism as a potential risk factor for cardiovascular disease in hemodialyzed patients. Cytokine 44:361–365CrossRefPubMedGoogle Scholar
  25. 25.
    Hassan AM, Nagy H, Mohamed WS (2010) Circulating MCP-1 level and 2518 gene polymorphism as a marker of nephropathy development in Egyptian patients. Egypt J Med Hum Genet 11:159–166CrossRefGoogle Scholar
  26. 26.
    Krüger B, Schröppel B, Ashkan R, Marder B, Zülke C, Murphy B, Krämer BK, Fischereder M (2002) A Monocyte chemoattractant protein-1 (MCP-1) polymorphism and outcome after renal transplantation. J Am Soc Nephrol 13:2585–2589CrossRefPubMedGoogle Scholar
  27. 27.
    Lehmann I, Fischereder M, Böhmig GA, Regele H, Exner M, Raith M, Weiss N, Segerer S (2008) The source matters: no impact of the CCL2/MCP-1-1-2518G polymorphism of the donor on renal allograft outcome during the first year after transplantation. Transplant Proc 40:3359–3361CrossRefPubMedGoogle Scholar
  28. 28.
    Tesch GH (2008) MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol 294:F697–F701CrossRefPubMedGoogle Scholar
  29. 29.
    Joo KW, Hwang YH, Kim JH, Oh KH, Kim H, Shin HD, Chung WK, Yang J, Park KS, Ahn C (2007) MCP-1 and RANTES Polymorphisms in Korean Diabetic End-Stage Renal Disease. J Korean Med Sci 22:611–615CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Moon JY, Jeong L, Lee S, Jeong K, Lee T, Ihm CG, Suh J, Kim J, Jung YY, Chung JH (2007) Association of polymorphisms in monocyte chemoattractant protein-1 promoter with diabetic kidney failure in Korean patients with type 2 diabetes mellitus. J Korean Med Sci 22:810–814CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Kouyama K, Miyake K, Zenibayashi M, Hirota Y, Teranishi T, Tamori Y, Kanda H, Sakaguchi K, Ohara T, Kasuga M (2008) Association of serum MCP-1 concentration and MCP-1 polymorphism with insulin resistance in Japanese individuals with obese type 2 diabetes. Kobe J Med Sci 53(6):345–354PubMedGoogle Scholar
  32. 32.
    Eriksson EE (2004) Mechanisms of leukocyte recruitment to atherosclerotic lesions: future prospects. Curr Opin Lipidol 15(5):553–558CrossRefPubMedGoogle Scholar
  33. 33.
    Bağcı G, Çinçin ZB, Daşdemir S, Özdemircan A, Karaali ZE, Çakmakoğlu B (2011) The effects of MCP-1 A-2518G and CCR2 G190A gene polymorphism on development of diabetic coronary artery disease. Deneysel Tıp Araştırma Enstitüsü Dergisi 1(2):9–13Google Scholar
  34. 34.
    Kaur R, Matharoo K, Arora P, Bhanwer AJ (2013) Association of -2518 A > G promoter polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene with type 2 diabetes and coronary artery disease. Genet Test Mol Biomark 17:750–755CrossRefGoogle Scholar
  35. 35.
    Tabara Y, Kohara K, Yamamoto Y, Igase M, Nakura J, Kondo I, Miki T (2003) Polymorphism of the monocyte chemoattractant protein (MCP-1) gene is associated with the plasma level of MCP-1 but not with carotid intima-media thickness. Hypertens Res 26:677–683CrossRefPubMedGoogle Scholar
  36. 36.
    Yuasa S, Maruyama T, Yamamoto Y, Hirose H, Kawai T, Matsunaga-Irie S, Itoh H (2009) MCP-1 gene A-2518G polymorphism and carotid artery atherosclerosis in patients with type 2 diabetes. Diabetes Res Clin Pract 86:193–198CrossRefPubMedGoogle Scholar
  37. 37.
    Alexander RW (1995) Hypertension and pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial inflammatory response. Hypertension 25:155–161CrossRefPubMedGoogle Scholar
  38. 38.
    Capers Q, Alexander RW, Lou P, De Leon H, Wilcox JN, Ishizaka N, Howard AB, Taylor WR (1997) Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats. Hypertension 30:1397–1402CrossRefPubMedGoogle Scholar
  39. 39.
    Penz P, Bucova M, Lietava J, Blazicek P, Paulovicova E, Mrazek F, Bernadic M, Buckingham TA, Petrek M (2010) MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects. Bratisl Lek Listy 111:420–425PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Binnur Bagci
    • 1
  • Gokhan Bagci
    • 2
  • Ferhan Candan
    • 3
  • Ozturk Ozdemir
    • 4
  • Ilhan Sezgin
    • 2
  1. 1.Department of Nutrition and Dietetics, Faculty of Health SciencesCumhuriyet UniversitySivasTurkey
  2. 2.Department of Medical Genetics, Faculty of MedicineCumhuriyet UniversitySivasTurkey
  3. 3.Division of Nephrology, Department of Internal Medicine, Faculty of MedicineCumhuriyet UniversitySivasTurkey
  4. 4.Department of Medical Genetics, Faculty of MedicineCanakkale On Sekiz Mart UniversityCanakkaleTurkey

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