Association of CCL5 rs2107538, and CCL2 rs3760396 Gene Polymorphisms with the Risk of Cardiovascular Disease
,
Abstract
Background: Chemokines are proinflammatory cytokines that play key roles in development of cardiovascular diseases (CVD). Chemokine-induced recruitment of peripheral leucocytes to tissues is a crucial step in the CVD progression. CC chemokines ligand 5, 2 (CCL5 and CCL2), have been characterized as emerging inflammatory biomarkers of atherosclerotic CVD. The aim of this study was to find out whether genetic polymorphisms of CCL5 -403 G>A (rs2107538) and CCL2 –927 G>C, (rs3760396) were associated with the risk of CVD.
Methods: In this case-control study, 500 Iranian individuals including 250 CVD patients and 250 healthy subjects as the control group participated in 2017. Genotyping of CCL5 -403 G>A and CCL2 –927 G>C polymorphisms were executed using Tetra-ARMS PCR method.
Results: At genotypic level both CCL5 -403 G>A and CCL2 –927 G>C polymorphisms were not associated with the risk of CVD (P>0.05), even after adjustment by age, sex, race, and history of hypertension, DM and smoking. However, the CCL2 –927 C allele was associated with an increased risk of CVD (OR=1.42, P=0.050) with a higher prevalence in CVD patient than in controls (17% vs. 12%). Moreover, the haplotype analysis revealed that CCL5/CCL2 haplotype (G/C) was a risk factor for CVD (OR=2.13, P=0.001), and that carriers of this haplotype were at 2.13-fold higher risk of CVD than subjects with G/G haplotype.
Conclusion: CCL2 –927 C variant and CCL5/CCL2 haplotype (G/C) were associated with susceptibility to CVD, and were risk factors for CVD in our population but more studies with large sample size are recommended.
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23. Magyar MT, Bereczki D, Csípő I, et al (2007). Elevated white blood cell count, CRP and fibrinogen levels are not associated with increased anti-endothelial and anti-ox-LDL antibody, MCP-1, and RANTES levels in early onset occlusive carotid artery disease. Cytokine, 37(1):44-50.
24. Iida Y, Xu B, Xuan H, et al (2013). Peptide Inhibitor of CXCL4–CCL5 Heterodimer Formation, MKEY, Inhibits Experimental Aortic Aneurysm Initiation and Progression. Arterioscler Thromb Vasc Biol, 33(4):718-26.
25. I Lu H, Wang J, Gao B, et al (2015). The association between the CC chemokine ligand 5-28C> G gene polymorphism and tuberculosis susceptibility. Saudi Med J, 36(12):1400-1407.
26. Zhernakova A, Alizadeh BZ, Eerligh P, et al (2006). Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes. Genes Immun, 7(7):544-9.
27. Jang Y, Chae JS, Hyun YJ, et al (2007). The RANTES− 403G> A promoter polymorphism in Korean men: association with serum RANTES concentration and coronary artery disease. Clin Sci (Lond), 113(8):349-56.
28. Cagnin S, Biscuola M, Patuzzo C, et al (2009). Reconstruction and functional analysis of altered molecular pathways in human atherosclerotic arteries. BMC Genomics, 10:13.
29. Qidwai, Tabish. (2016). Chemokine genetic polymorphism in human health and disease. Immunol Lett, 176: 128-38.
30. Vogiatzi K, Voudris V, Apostolakis S, et al (2009). Genetic diversity of RANTES gene promoter and susceptibility to coronary artery disease and restenosis after percutaneous coronary intervention. Thromb Res, 124(1):84-9.
2. Chapman MJ, Ginsberg HN, Amarenco P, et al (2011).Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J, 32(11):1345-61.
3. Jones KL, Maguire JJ, Davenport AP (2011). Chemokine receptor CCR5: from AIDS to atherosclerosis. Br J Pharmacol, 162(7):1453-69
4. Rothenbacher D, Müller-Scholze S, Herder C, et al (2006). Differential expression of chemokines, risk of stable coronary heart disease, and correlation with established cardiovascular risk markers. Arterioscler Thromb Vasc Biol, 26(1):194-9.
5. Niu J, Kolattukudy PE (2009). Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications. Clin Sci (Lond), 117(3):95-109.
6. van Wijk DF, van Leuven SI, Sandhu MS, et al (2010). Chemokine ligand 2 genetic variants, serum monocyte chemoattractant protein-1 levels, and the risk of coronary artery disease. Arterioscler Thromb Vasc Biol, 30(7):1460-1466.
7. Duell EJ, Casella DP, Burk RD, et al (2006). Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev,15(4):726-31.
8. Böger CA, Fischereder M, Deinzer M, et al (2005). RANTES gene polymorphisms predict all-cause and cardiac mortality in type 2 diabetes mellitus hemodialysis patients. Atherosclerosis, 183(1):121-9.
9. Aukrust P, Ueland T, Müller F, et al (1998). Elevated circulating levels of CC chemokines in patients with congestive heart failure. Circulation, 97(12):1136-43.
10. Herder C, Peeters W, Illig T, et al (2011). RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies. PLoS One, 6(12):e25734.
11. Liu J, Jia YJ, Li XL, et al (2012). RANTES gene G-403A polymorphism and coronary artery disease: a meta analysis of observational studies. PLoS One, 7(10):e47211.
12. Simeoni E, Winkelmann BR, Hoffmann MM, et al (2004). Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis. Eur Heart J, 25(16):1438-46.
13. Nyquist P, Zhang J, De Graba TJ (2010). The–928 G/C and–362 G/C Single-Nucleotide Polymorphisms in the Promoter of MCP-1: Increased Transcriptional Activity and Novel Binding Sites. Cerebrovasc Dis, 29(3):242-7.
14. Brenner D, Labreuche J, Touboul PJ, et al (2006). Cytokine polymorphisms associated with carotid intima-media thickness in stroke patients. Stroke, 37(7):1691-6.
15. McDermott DH, Yang Q, Kathiresan S, et al (2005). CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation, 112(8):1113-20.
16. Park HJ, Yun DH, Kim SK, et al (2013). Association of CXCL 1 promoter polymorphism with ischaemic stroke in K orean population. Int J Immunogenet, 40(4):306-10.
17. Lin DY, Huang BE (2007). The use of inferred haplotypes in downstream analyses. Am J Hum Genet, 80(3): 577–579.
18. Navratilova Z (2006). Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 150(2):191-204.
19. Ye H, Li X, Wang L, et al (2013). Genetic associations with coronary heart disease: meta-analyses of 12 candidate genetic variants. Gene, 531(1):71-7.
20. Tereshchenko IP, Petrkova J, Voevoda MI, et al (2011). CCL5/RANTES gene polymorphisms in Slavonic patients with myocardial infarction. Mediators of Inflammation, 2011(12):525691.
21. Parissis JT, Adamopoulos S, Venetsanou KF, et al (2002). Serum profiles of CC chemokines in acute myocardial infarction: possible implication in postinfarction left ventricular remodeling. J Interferon Cytokine Res, 22(2):223-9.
22. Pawlak K, Pawlak D, Brzosko S, et al (2006). Carotid atherosclerosis is associated with enhanced β-chemokine levels in patients on continuous ambulatory peritoneal dialysis. Atherosclerosis, 186(1):146-51.
23. Magyar MT, Bereczki D, Csípő I, et al (2007). Elevated white blood cell count, CRP and fibrinogen levels are not associated with increased anti-endothelial and anti-ox-LDL antibody, MCP-1, and RANTES levels in early onset occlusive carotid artery disease. Cytokine, 37(1):44-50.
24. Iida Y, Xu B, Xuan H, et al (2013). Peptide Inhibitor of CXCL4–CCL5 Heterodimer Formation, MKEY, Inhibits Experimental Aortic Aneurysm Initiation and Progression. Arterioscler Thromb Vasc Biol, 33(4):718-26.
25. I Lu H, Wang J, Gao B, et al (2015). The association between the CC chemokine ligand 5-28C> G gene polymorphism and tuberculosis susceptibility. Saudi Med J, 36(12):1400-1407.
26. Zhernakova A, Alizadeh BZ, Eerligh P, et al (2006). Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes. Genes Immun, 7(7):544-9.
27. Jang Y, Chae JS, Hyun YJ, et al (2007). The RANTES− 403G> A promoter polymorphism in Korean men: association with serum RANTES concentration and coronary artery disease. Clin Sci (Lond), 113(8):349-56.
28. Cagnin S, Biscuola M, Patuzzo C, et al (2009). Reconstruction and functional analysis of altered molecular pathways in human atherosclerotic arteries. BMC Genomics, 10:13.
29. Qidwai, Tabish. (2016). Chemokine genetic polymorphism in human health and disease. Immunol Lett, 176: 128-38.
30. Vogiatzi K, Voudris V, Apostolakis S, et al (2009). Genetic diversity of RANTES gene promoter and susceptibility to coronary artery disease and restenosis after percutaneous coronary intervention. Thromb Res, 124(1):84-9.
| Files | ||
| Issue | Vol 50 No 7 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v50i7.6634 | |
| Keywords | ||
| CC chemokines ligand 5 2 (CCL5 and CCL2) Cardiovascular disease Genetic polymorphism | ||
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How to Cite
1.
Mohtavinejad N, Nakhaee A, Harati H, Gholipour N, Mahmoodzade Y. Association of CCL5 rs2107538, and CCL2 rs3760396 Gene Polymorphisms with the Risk of Cardiovascular Disease. Iran J Public Health. 2021;50(7):1436-1444.
