Molecular Biology Reports

, Volume 42, Issue 5, pp 997–1012 | Cite as

The associations between the MCP-1 −2518 A/G polymorphism and ischemic heart disease and ischemic stroke: a meta-analysis of 28 research studies involving 21,524 individuals

  • Gaojun Cai
  • Bifeng Zhang
  • Weijin Weng
  • Ganwei Shi
  • Zhiying Huang


Epidemiologic studies have been performed to explore the relationship between MCP-1 polymorphism and ischemic heart disease (IHD) and ischemic stroke (IS). But, the results are not consistent. Because of the poor effect of each individual study, we’ve performed a systematic review and a meta-analysis. A comprehensive search was carried out from PubMed, Embase, Foreign Medical Journal Service (FMJS), China National Knowledge Infrastructure and Wanfang Data. Odds ratios (OR) with 95 % confidence interval (CI) were used to evaluate the strength of associations between the MCP-1 A-2518G polymorphism (rs1024611) and IHD and IS susceptibilities. The pooled OR was calculated by the allelic model (G vs A), the additive model (GG vs AA), the dominant model (GG+GA vs AA) and the recessive model (GG vs AA+GA), respectively. The homogeneity among studies was checked using Cochrane Q statistic. The stability of results was checked by one-way sensitivity analysis. The publication bias between studies was examined by Begg’s funnel plots and Egger’s test. 28 eligible case–control studies met all the criteria and were involved in the present meta-analysis, including a total of 8,901 cases and 12,623 controls. Overall, the MCP-1 A-2518G polymorphism was significantly associated with the IHD susceptibility. The pooled OR was 1.27 (95 % CI 1.09–1.48, P = 0.002) in the dominant model, 1.20 (95 % CI 1.07–1.35, P = 0.001) in the allelic model, 1.25 (95 % CI 1.05–1.50, P = 0.015) in the recessive model and 1.39 (95 % CI 1.10–1.75, P = 0.005) in the additive model. At the same time, the MCP-1 A-2518G polymorphism was significantly associated with the IS susceptibility. The pooled OR was 1.72 (95 % CI 1.12–2.65, P = 0.013) in the dominant model, 1.39 (95 % CI 1.12–1.74, P = 0.003) in the allelic model, 1.59 (95 % CI 1.30–1.93, P = 0.000) in the recessive model, and 2.33 (95 % CI 1.76–3.08, P = 0.000) in the additive model, respectively. No significant publication bias was found in the present meta-analysis. The results of the present meta-analysis suggest that MCP-1 gene A-2518G polymorphism may be associated with the IHD and IS susceptibilities. But the positive result exists in relatively small sample size subgroup.


MCP-1 Polymorphism Ischemic heart disease Ischemic stroke Meta-analysis 


  1. 1.
    Nelken NA, Coughlin SR, Gordon D, Wilcox JN (1991) Monocyte chemoattractant protein-1 in human atheromatous plaques. J Clin Invest 88:1121–1127CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Gonzalez-Quesada C, Frangogiannis NG (2009) Monocyte chemoattractant protein-1/CCL2 as a biomarker in acute coronary syndromes. Curr Atheroscler Rep 11:131–138CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Robinson SC, Scott KA, Balkwill FR (2002) Chemokine stimulation of monocyte matrix metalloproteinase-9 requires endogenous TNF-alpha. Eur J Immunol 32:404–412CrossRefPubMedGoogle Scholar
  4. 4.
    Rovin BH, Lu L, Saxena R (1999) A novel polymorphism in the MCP-1gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun 259:344–348CrossRefPubMedGoogle Scholar
  5. 5.
    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. Arthr Rheum 44:2211–2212CrossRefGoogle Scholar
  6. 6.
    Walczak A, Przybylowska K, Sygut A, Dziki L, Chojnacki C, Chojnacki J, Dziki A, Majsterek I (2012) The -2518 A/G MCP-1 polymorphism as a risk factor of inflammatory bowel disease. Pol Przegl Chir 84(5):238–241PubMedGoogle Scholar
  7. 7.
    Karadeniz M, Erdogan M, Cetinkalp S, Berdeli A, Eroglu Z, Ozgen AG (2010) Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy. Endocrine 37:513–517CrossRefPubMedGoogle Scholar
  8. 8.
    Ozyurek AR, Gurses D, Ulger Z, Levent E, Bakiler AR, Berdeli A (2007) Allelic frequency of the MCP-1 promoter −2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis. Clin Rheumatol 26:546–550CrossRefPubMedGoogle Scholar
  9. 9.
    Szalai C, Duba J, Prohaszka Z, Kalina A, Szabo T, Nagy B, Horvath L, Csaszar A (2001) Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 −2518 G/G genotype in CAD patients. Atherosclerosis 158:233–239CrossRefPubMedGoogle Scholar
  10. 10.
    McDermott DH, Yang Q, Kathiresan S, Cupples LA, Massaro JM, Keaney JF Jr, Larson MG, Vasan RS, Hirschhorn JN, O’Donnell CJ, Murphy PM, Benjamin EJ (2005) CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation 112:1113–1120CrossRefPubMedGoogle Scholar
  11. 11.
    Kim MP, Wahl LM, Yanek LR, Becker DM, Becker LC (2007) A monocyte chemoattractant protein-1 gene polymorphism is associated with occult ischemia in a high-risk asymptomatic population. Atherosclerosis 193:366–372CrossRefPubMedGoogle Scholar
  12. 12.
    Jemaa R, Rojbani H, Kallel A, Ben Ali S, Feki M, Chabrak S, Elasmi M, Taieb SH, Sanhaji H, Souheil O, Mechmeche R, Kaabachi N (2008) Association between the −2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and myocardial infarction in Tunisian patients. Clin Chim Acta 390:122–125CrossRefPubMedGoogle Scholar
  13. 13.
    Bucova M, Lietava J, Mrazek F, Petrkova J, Bernadic M, Buckingham T, Petrek M (2008) Association of chronic stable angina pectoris with MCP-1-2518 A/G single nucleotide polymorphism in the Slovak population. Clin Chim Acta 392:71–72CrossRefPubMedGoogle Scholar
  14. 14.
    Buraczynska M, Bednarek-Skublewska A, 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
  15. 15.
    Bucova M, Lietava J, Penz P, Mrazek F, Petrkova J, Bernadic M, Petrek M (2009) Association of MCP-1 −2518 A/G single nucleotide polymorphism with the serum level of CRP in slovak patients with ischemic heart disease, angina pectoris, and hypertension. Mediat Inflamm 2009:390951CrossRefGoogle Scholar
  16. 16.
    Bucova M, Lietava J, Mrazek F, Petrkova J, Penz P, Bernadic M, Buckingham TA, Petrek M (2009) The MCP-1 −2518(A/G) single nucleotide polymorphism is associated with ischemic heart disease and myocardial infarction in men in the Slovak population. Bratisl Lek Listy 110:385–389PubMedGoogle Scholar
  17. 17.
    El Mahgoub IR, Afify RA, Aal AA, Beda DG (2011) Association between the monocyte chemoattractant protein-1 −2518G/A gene polymorphism and acute myocardial infarction patients among Egyptian population. Blood Coagul Fibrinolysis 22:8–13CrossRefGoogle Scholar
  18. 18.
    Lin HL, Ueng KC, Hsieh YS, Chiang WL, Yang SF, Chu SC (2012) Impact of MCP-1 and CCR-2 gene polymorphisms on coronary artery disease susceptibility. Mol Biol Rep 39:9023–9030CrossRefPubMedGoogle Scholar
  19. 19.
    Wang QB, Zhang YL (2012) Correlation of MCP-1 −2518A/G gene polymorphism with acute myocardial infarction. Chin Gen Pract 15:1600–1602 (Chinese)Google Scholar
  20. 20.
    Yang LX, Guo RW, Qi F, Wang XM, Guo CM, Ren L, Xu AF (2012) MCP-1-2518G/A gene ploymorphisms and coronary atherosclerotic heart disease. Chin J Mult Organ Dis Elder 11:273–276 (Chinese)Google Scholar
  21. 21.
    Flex A, Gaetani E, Papaleo P, Straface G, Proia AS, Pecorini G, Tondi P, Pola P, Pola R (2004) Proinflammatory genetic profiles in subjects with history of ischemic stroke. Stroke 35:2270–2275CrossRefPubMedGoogle Scholar
  22. 22.
    Brenner D, Labreuche J, Touboul PJ, Schmidt-Petersen K, Poirier O, Perret C, Schonfelder J, Combadiere C, Lathrop M, Cambien F, Brand-Herrmann SM, Amarenco P (2006) Cytokine polymorphisms associated with carotid intima-media thickness in stroke patients. Stroke 37:1691–1696CrossRefPubMedGoogle Scholar
  23. 23.
    Chen Shiyan, Zhang ZJ, Wu XL, et al (2007) Study the relationship between the monocyte chemoattractant protein-1 gene -2518G/A polymorphism and cerebral infarction of Han population in Chinese Hunan district. J Clin Neurol 20:167–169 (Chinese)Google Scholar
  24. 24.
    Yang YX, Zhang ML, Liu B (2010) Correlational study between polymorphism of monocyte chemoattractant protein-1(MCP-1) gene-2518G/A and cerebral infarction. J Apoplexy Nerv Dis 27:742–744 (Chinese)Google Scholar
  25. 25.
    Buraczynska K, Luchowski P, Wojczal J, Ksiazek A, Stelmasiak Z (2010) Monocyte chemoattractant protein (MCP-1) A-2518G gene polymorphism in stroke patients with different comorbiditie. Clin Biochem 43:1421–1426CrossRefPubMedGoogle Scholar
  26. 26.
    Liang HF, Wang H, Zhang YX, Zhang HL, Yu J (2011) Study on relationship between monocyte chemoattractant protein-1 gene -2518G/A polymorphism and cerebral infarction of Hasake population in Chinese Xinjiang district. Clin Focus 26:2025–2028. (Chinese)Google Scholar
  27. 27.
    Simeoni E, Winkelmann BR, Hoffmann MM, Fleury S, Ruiz J, Kappenberger L, Marz W, Vassalli G (2004) Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis. Eur Heart J 25:1438–1446CrossRefPubMedGoogle Scholar
  28. 28.
    McGlinchey PG, Spence MS, Patterson CC, Allen AR, Murphy G, Belton C, McKeown PP (2004) Lack of association between the −2518G/A polymorphism of the MCP-1 gene and ischaemic heart disease: a family-based investigation. Tissue Antigens 64:199–203CrossRefPubMedGoogle Scholar
  29. 29.
    Cermakova Z, Petrkova J, Arakelyan A, Drabek J, Mrazek F, Lukl J, Petrek M (2005) The MCP-1 -2518 (A to G) single nucleotide polymorphism is not associated with myocardial infarction in the Czech population. Int J Immunogenet 32:315–318CrossRefPubMedGoogle Scholar
  30. 30.
    Iwai N, Kajimoto K, Kokubo Y, Okayama A, Miyazaki S, Nonogi H, Goto Y, Tomoike H (2006) Assessment of genetic effects of polymorphisms in the MCP-1 gene on serum MCP-1 levels and myocardial infarction in Japanese. Circ J 70:805–809CrossRefPubMedGoogle Scholar
  31. 31.
    Bjarnadottir K, Eiriksdottir G, Aspelund T, Gudnason V (2006) Examination of genetic effects of polymorphisms in the MCP-1 and CCR2 genes on MI in the Icelandic population. Atherosclerosis 188:341–346CrossRefPubMedGoogle Scholar
  32. 32.
    Park S, Youn JC, Shin DJ, Park CM, Kim JS, Ko YG, Choi D, Ha JW, Jang Y, Chung N (2007) Genetic polymorphism in the pregnancy-associated plasma protein-A associated with acute myocardial infarction. Coron Artery Dis 18:417–422CrossRefPubMedGoogle Scholar
  33. 33.
    Cam SF, Sekuri C, Sagcan A, Ercan E, Tengiz I, Alioglu E, Berdeli A (2008) Effect of monocyte chemoattractant protein-1(MCP-1) gene polymorphism in Turkish patients with premature coronary artery disease. Scand J Clin Lab Invest 68:801–805CrossRefPubMedGoogle Scholar
  34. 34.
    Zhang X, Han Y, Kang J, Yan C (2009) A monocyte chemoattractant protein-1 gene polymorphism is not associated with coronary artery disease in a Han Chinese population. Clin Chim Acta 403:241–243CrossRefPubMedGoogle Scholar
  35. 35.
    Zhong C, Luzhan Z, Genshan M, Jiahong W, Xiaoli Z, Qi Q (2010) Monocyte chemoattractant protein-1-2518 G/A polymorphism plasma levels, and premature stable coronary artery disease. Mol Biol Rep 37:7–12CrossRefPubMedGoogle Scholar
  36. 36.
    van Wijk DF, van Leuven SI, Sandhu MS, Tanck MW, Hutten BA, Wareham NJ, Kastelein JJ, Stroes ES, Khaw KT, Boekholdt SM (2010) Chemokine ligand 2 genetic variants, serum monocyte chemoattractant protein-1 levels, and the risk of coronary artery disease. Arterioscler Thromb Vasc Biol 30:1460–1466CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Shi GW, He GP, Cai GJ, Qi CP, Gao L, Qi M, Shen DD, Qian ZH, Xu LH (2012) Correlation between polymorphism of monocyte chemoattractant protein-1 gene A-2518G single nucleotide and acute coronary syndrome. Chin J Emerg Med 21:687–693. (Chinese)Google Scholar
  38. 38.
    Dai YM, Guan GY, Han Hui, et al (2006) Analysis of the MCP-1 promoter-2518A/G gene polymorphism in cerebral infarction patients. J Apoplexy Nerv Dis 23:152–154. (Chinese)Google Scholar
  39. 39.
    World Health Organization (2008) The top 10 causes of death. WHO, GenevaGoogle Scholar
  40. 40.
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefPubMedGoogle Scholar
  41. 41.
    DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114CrossRefPubMedGoogle Scholar
  42. 42.
    Wang Y, Zhang W, Li S, Song W, Chen J, Hui R (2011) Genetic variants of the monocyte chemoattractant protein-1 gene and its receptor CCR2 and risk of coronary artery disease: a meta-analysis. Atherosclerosis 219:224–230CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Gaojun Cai
    • 1
  • Bifeng Zhang
    • 2
  • Weijin Weng
    • 1
  • Ganwei Shi
    • 1
  • Zhiying Huang
    • 3
  1. 1.Department of CardiologyWujin Hospital, Affiliated to Jiangsu UniversityChangzhouChina
  2. 2.Department of Pathology and Molecular MedicineMcMaster UniversityHamiltonCanada
  3. 3.Department of PediatricsNo. 2 Hospital of ChangzhouChangzhouChina

Personalised recommendations