Iranian Journal of Pathology

Evaluation the -174G>C Genetic Polymorphism of Interleukin-6 in Iranian Patients with Chronic Lymphocytic Leukemia

Document Type : Original Research

Authors

Zakieh Rostamzadeh Khameneh 1
Mahshid Mohammadian 2
Ali Eishi Oskuie 3
Rahim Asghari 4
Mohadeseh Nemati 2

1 Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran

2 Department of Clinical Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

3 Department of Hematology and Medical Oncology, Urmia University of Medical Sciences, Urmia, Iran

4 Department of Internal Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

https://doi.org/10.30699/ijp.2023.544600.2790
Abstract
Background & Objective: Interleukin-6 (IL-6) is involved in inflammation and has a significant role in chronic lymphocytic leukemia (CLL) progression. Accordingly, IL-6 level may increase in CLL-affected patients compared to healthy individuals. The -174G>C single nucleotide polymorphism (SNP) in IL-6 promoter region has been related to differences in IL-6 transcription. Therefore, we investigated the possible association of IL-6 polymorphism with CLL.
Methods: We examined the -174G>C SNP in IL-6 gene and studied its possible relationship with CLL in affected patients and in healthy controls using Amplification Refractory Mutation System- polymerase chain reaction genotyping method.  IL-6 plasma level was measured in both studied groups.
Results: According to the results, IL-6 mean plasma concentration was increased significantly in the CLL patients compared to the controls. However, 174G>C genotype of the IL-6 gene was not associated with CLL. Furthermore, there were no significant differences in the distribution of allele and genotype frequencies between the CLL-affected patients and the controls (P>0.05).
Conclusion: Our study showed that -174G>C SNP in promotor of IL-6 gene could not be considered a risk factor for CLL. Larger prospective studies should be performed to confirm our results.

Keywords

Chronic lymphocytic leukemia, Interleukin-6
Polymorphism

Subjects

  1. Hulkkonen J, Vilpo J, Vilpo L, Koski T, Hurme M. Interleukin-1 beta, interleukin-1 receptor antagonist and interleukin-6 plasma levels and cytokine gene polymorphisms in chronic lymphocytic leukemia: correlation with prognostic parameters. Haematologica. 2000; 85(6):600-6. [PMID]
  2. Salari N, Mansouri K, Hosseinian-Far A, Ghasemi H, Mohammadi M, Jalali R, et al. The effect of polymorphisms (174G> C and 572C> G) on the Interleukin-6 gene in coronary artery disease: a systematic review and meta-analysis. Genes Environ. 2021; 12; 43(1):1. [DOI:10.1186/s41021-021-00172-8] [PMID]
  3. Tian G, Mi J, Wei X, Zhao o, Qiao L, Yang C, et al. Circulating interleukin-6 and cancer: A meta-analysis using Mendelian randomization. Sci Rep. 2015; 5, 11394. [DOI:10.1038/srep11394] [PMID]
  4. Ennas MG, Moore PS, Zucca M, Angelucci E, Cabras MG, Melis M, et al. Interleukin-1B (IL1B) and interleukin-6 (IL6) gene polymorphisms are associated with risk of chronic lymphocytic leukaemia. Hematol Oncol. 2008; 26(2):98-103. [DOI:10.1002/hon.843] [PMID]
  5. Ma H, Sun G, Wang W, Zhou Y, Liu D, Tong Y, Lu Z. Association Between Interleukin-6 -572 C>G and -174 G>C Polymorphisms and Hypertension: A Meta-analysis of Case-control Studies. Medicine (Baltimore). 2016; 95(2):e2416. [DOI:10.1097/MD.0000000000002416] [PMID]
  6. Zhang X, Liu RY, Lei Z, Zhu Y, Huang JA, Jiang X, et al. Genetic variants in interleukin-6 modified risk of obstructive sleep apnea syndrome. Int J Mol Med. 2009; 2:485-93. [DOI:10.3892/ijmm_00000155] [PMID]
  7. Hashemi M, Jalali Kondori B, Esmaeili Gouvarchin Ghaleh H, Rostami S. Association between rs 1800561 CD38 Gene Polymorphism and Chronic Lymphocytic Leukemia Risk. J Mazandaran Univ Med Sci. 2020; 30 (191):102-8.
  8. Peng X., Shi J., Sun W., Ruan X., Guo Y., Zhao L., Wang J., Li B. Genetic polymorphisms of IL-6 promoter in cancer susceptibility and prognosis: a meta-analysis. Oncotarget. 2018; 9: 12351-64. [DOI:10.18632/oncotarget.24033] [PMID]
  9. Allegra A, Musolino C, Tonacci A, Pioggia G, Casciaro M, Gangemi S. Clinico-Biological Implications of Modified Levels of Cytokines in Chronic Lymphocytic Leukemia: A Possible Therapeutic Role. Cancers (Basel). 2020;12(2):524. [DOI:10.3390/cancers12020524] [PMID]
  10. Popko K, Gorska E, Demkow U. Influence of interleukin-6 and G174C polymorphism in IL-6 gene on obesity and energy balance. Eur J Med Res. 2010; 15 Suppl 2(Suppl 2):123-7. [DOI:10.1186/2047-783X-15-S2-123] [PMID]
  11. Walch K, Grimm C, Zeillinger R, Huber JC, Nagele F, Hefler LA. A common interleukin-6 gene promoter polymorphism influences the clinical characteristics of women with polycystic ovary syndrome. Fertil Steril. 2004; 81(6):1638-41. [DOI:10.1016/j.fertnstert.2004.01.021] [PMID]
  12. Fishman D,Faulds G,Jeffrey R, Mohamed-Ali V, Yudkin J.S, Humphries S, 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: 1369-76. [DOI:10.1172/JCI2629] [PMID]
  13. Ramis IB, Vianna JS, Gonçalves CV, von Groll A, Dellagostin OA, da Silva PEA. Polymorphisms of the IL-6, IL-8 and IL-10 genes and the risk of gastric pathology in patients infected with Helicobacter pylori. J Microbiol Immunol Infect. 2017; 50(2):153-9. [DOI:10.1016/j.jmii.2015.03.002] [PMID]
  14. DeMichele A, Martin AM, Mick R, Gor P, Wray L, Klein-Cabral M, Athanasiadis G, Colligan T, Stadtmauer E, Weber B. Interleukin-6 -174G-->C polymorphism is associated with improved outcome in high-risk breast cancer. Cancer Res. 2003; 63:8051-6.
  15. Ahirwar D, Kesarwani P, Manchanda PK, Mandhani A, Mittal RD. Anti- and proinflammatory cytokine gene polymorphism and genetic predisposition: association with smoking, tumor stage and grade, and bacillus Calmette-Guérin immunotherapy in bladder cancer. Cancer Genet Cytogenet. 2008; 184(1):1-8. [DOI:10.1016/j.cancergencyto.2008.02.015] [PMID]
  16. Lagmay JP, London WB, Gross TG, Termuhlen A, Sullivan N, Axel A, Mundy B, Ranalli M, Canner J, McGrady P, Hall B. Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor). Clin Cancer Res. 2009;15:5234-9. [DOI:10.1158/1078-0432.CCR-08-2953] [PMID]
  17. Gomes M, Coelho A, Araújo A, Azevedo A, Teixeira AL, Catarino R, Medeiros R. IL-6 polymorphism in non-small cell lung cancer: a prognostic value? Tumour Biol. 2015; 36(5):3679-84. [DOI:10.1007/s13277-014-3006-6] [PMID]
  18. Totaro F, Cimmino F, Pignataro P, Acierno G, De Mariano M, Longo L, et al. Impact of interleukin-6 -174 G>C gene promoter polymorphism on neuroblastoma. PLoS One. 2013; 8(10):e76810. [DOI:10.1371/journal.pone.0076810] [PMID]
  19. Zhai K, Yang Y, Gao ZG, Ding J. Interleukin-6-174G>C gene promoter polymorphism and prognosis in patients with cancer. Oncotarget. 2017; 8(27):44490-7. [DOI:10.18632/oncotarget.17771] [PMID]
  20. Lai R, O'Brien S, Maushouri T, Rogers A, Kantarjian H, Keating M, et al. Prognostic value of plasma interleukin-6 levels in patients with chronic lymphocytic leukemia. Cancer. 2002 Sep 1; 95(5):1071-5. [DOI:10.1002/cncr.10772] [PMID]
  21. Reittie J, Yong K, Panayiotidus P, Hoffbrand A. Interleukin-6 inhibits apoptosis and tumor necrosis factor induced proliferation of B-chronic lymphocytic leukemia. LeukLymphoma. 1996; 22: 83- 90. [DOI:10.3109/10428199609051732] [PMID]
  22. Fayad L, Keating MJ, Reuben JM, O'Brien S, Lee BN, Lerner S, Kurzrock R. Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: correlation with phenotypic characteristics and outcome. Blood. 2001 Jan 1;97(1):256-63. [DOI:10.1182/blood.V97.1.256] [PMID]
  23. Nakajima K, Yamanaka Y, Nakae K, Kojima H, Ichiba M, Kiuchi N, et al. A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO J. 1996; 15(14):3651-8. [DOI:10.1002/j.1460-2075.1996.tb00734.x] [PMID]
  24. Belluco C, Olivieri F, Bonafè M, Giovagnetti S, Mammano E, Scalerta R, et al. -174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res. 2003; 9(6):2173-6. [PMID]
  25. Mandal S, Abebe F, Chaudhary J. -174G/C polymorphism in the interleukin-6 promoter is differently associated with prostate cancer incidence depending on race. Genet Mol Res. 2014; 13(1):139-51. [DOI:10.4238/2014.January.10.5] [PMID]
  26. Liu RT, Wang XX, Sun JR, Gao N, Yu WZ. Correlations of IL-6 and IL-10 gene polymorphisms with childhood acute lymphoblastic leukemia. Eur Rev Med Pharmacol Sci. 2020; 24(15):8048-56. [DOI: 26355/eurrev_202008_22488] [PMID]
  27. Alizadeh S, Bohloli S, Abedi A, Mousavi S H, Dargahi H, Jafarzadeh B, Hamrang N, Imani A. Investigation of Leptin, Leukemia Inhibitory Factor (LIF), and IL-6 Serum Levels in Myeloid Leukemia. IJBC. 2010; 2 (4).
  28. Zheng C, Huang DR, Bergenbrant S, Sundblad A, Osterborg A, Björkholm M, Holm G, Yi Q. 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(1):39-45. [DOI:10.1046/j.1365-2141.2000.01963.x] [PMID]
Iranian Journal of Pathology
Volume 18, Issue 4
Autumn 2023
Pages 392-397

  • Receive Date 30 January 2023
  • Revise Date 26 August 2022
  • Accept Date 22 June 2023

Home

Guide for Authors

Submit Manuscript

Contact Us