The Pattern of Methylation and Polymorphism in Interleukin-6 Promoter Gene Are Related to the Development of Rheumatoid Arthritis?
-
Isaura Isabelle Fonseca Gomes-Silva
,
Eliezer Rushansky
,
Francisco Geraldo Carvalho-Neto
,
Amanda Virginia Batista Vieira
,
Maria Helena Queiroz de Araujo Mariano
,
Paulo Roberto Eleutério de Souza
,
Martín Alejandro Montes
,
Maria Mascena Diniz Maia
Abstract
Rheumatoid Arthritis (RA) is a complex disease with higher level of IL-6. In order to elucidate the alterations related to IL-6 gene in RA, we evaluated the -174 G/C IL-6 gene polymorphism and methylation pattern of its promoter. A total of 120 RA patients and 120 healthy controls were recruited for polymorphism analysis, and 30 individuals of both groups were randomly selected for methylation analysis. The IL-6 gene polymorphism was analyzed by PCR-RFLP and methylation pattern was analyzed by MSP-PCR. Regarding IL-6 gene polymorphism, no significant difference was found between RA patients and controls (P>0.05). For DNA, two CpG regions of IL-6 promoter gene was analyzed. The first region (−1069, −1061, −1057 and −1001 CpG) did not show significant differences, whereas the second region (−628, −610, −574 and −491 CpG) showed a significant hypermethylated status (P=0.0004) in RA patients as compared with controls.These results, suggest a possible relationship between methylation pattern and the susceptibility to RA in our studied population.
Trenkmann M, Brock M, Ospelt C, et al. Epigenetics in Rheumatoid Arthritis. Clin. Rev. Allergy Immunol 2010; 39(1): 10–19.
Trajkov D, Mishevska-Perchinkova S, Karadzova-Stojanoska A, et al. Association of 22 cytokine gene polymorphisms with rheumatoid arthritis in population of ethnic Macedonians. Clin Rheumatol 2009; 28(11): 1291–1300.
Gierut A, Perlman H, Pope RM. Innate Immunity and Rheumatoid Arthritis. Rheum. Dis Clin N Am 2010; 36(2): 271–296.
Yoshida Y, Tanaka T. Interleukin 6 and Rheumatoid Arthritis. Bio Med Res Int 2014; 1–12.
Le Goff B, Blanchard F, Berthelot JM, et al. Role for interleukin-6 in structural joint damage and systemic bone loss in rheumatoid arthritis. Joint Bone Spine 2010; 77(3): 201–205.
Solus JF, Chung CP, Oeser A, et al. Genetics of serum concentration of IL-6 and TNFα in systemic lupus erythematosus and rheumatoid arthritis: a candidate gene analysis. Clin Rheumatol 2015; 34(8):1375–1382.
Li X, Chai W, Ni M, et al. The Effects of Gene Polymorphisms in Interleukin-4 and Interleukin-6 on the Susceptibility of Rheumatoid Arthritis in a Chinese Population. Bio Med Res 2014; 1–5.
Angelo HD, Gomes Silva IIF, Oliveira RDR, et al. Interleukin-18, interleukin-12B and interferon-γ gene polymorphisms in Brazilian patients with rheumatoid arthritis: a pilot study: IL-18, IL-12B and IFN-γ gene polymorphisms and rheumatoid arthritis. Tissue Antigens 2015; 86(4): 276–278.
Bennermo M. Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases? Clin Chem 2004; 50(11): 2136–2140.
Col-Araz N, Pehlivan S, Baspinar O. et al. Role of cytokine gene (IFN-γ, TNF-α, TGF-β1, IL-6, and IL-10) polymorphisms in pathogenesis of acute rheumatic fever in Turkish children. Eur J Pediatr 2012; 171(7):1103–1108.
Pola E, Papaleo P, Pola R, et al. Interleukin-6 gene polymorphism and risk of osteoarthritis of the hip: a case–control study. Osteoarthritis Cartilage 2005; 13(11):1025–1028.
Nile CJ, Read RC, Akil M, et al. Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum 2008; 58(9): 2686–2693.
Stefani FA, Viana MB, Dupim AC, et al. Expression, polymorphism and methylation pattern of interleukin-6 in periodontal tissues. Immunobiology 2013; 218(7): 1012–1017.
Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31(3):315–24.
Pappas JJ, Toulouse A, Bradley WEC. The bisulfite genomic sequencing protocol. Adv Lung Cancer 2013; 2(1): 21–25.
Asano NM, Angelo HD, da Silva HA, et al. Interleukin-6 promoter polymorphisms −174 G/C in Brazilian patients with systemic lupus erythematosus. Hum Immunol 2013; 74(9): 1153–1156.
Team RC, R. A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2013. ((Accessed March 4, 2017, at http. www. R-project. org).
Zavaleta-Muñiz SA, Martín-Márquez BT, Gonzalez-Lopez L, et al. Patients The −174G/C and −572G/C Interleukin 6 Promoter Gene Polymorphisms in Mexican with Rheumatoid Arthritis: A Case-Control Study. Clin Dev Immunol 2013;2013: 1–5.
Palomino-Morales R, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, et al. Interleukin-6 gene-174 promoter polymorphism is associated with endothelial dysfunction but not with disease susceptibility in patients with rheumatoid arthritis. Clin Exp Rheumatol 2009; 27(6): 964–970.
Arman A, Coker A, Sarioz O, et al. Lack of association between IL-6 gene polymorphisms and rheumatoid arthritis in Turkish population. Rheumatol Int 2012; 32(7): 2199–2201.
Amr K, El-Awady R, Raslan H. Assessment of the −174G/C (rs1800795) and −572G/C (rs1800796) Interleukin 6 Gene Polymorphisms in Egyptian Patients with Rheumatoid Arthritis. Open Access Maced J Med Sci 2016; 4(4): 574-577.
Dar SA, Haque S, Mandal RK, et al. Interleukin-6-174G/C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis. Autoimmunity 2016; 1–12.
Ishida K, Kobayashi T, Ito S, et al. Interleukin-6 Gene Promoter Methylation in Rheumatoid Arthritis and Chronic Periodontitis. J Periodontol 2012; 83(7): 917–925.
Kojima A, Kobayashi T, Ito S, et al. Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis. J Periodontal Res 2016; 51(3): 350–358.
Na YK, Hong HS, Lee WK, et al. Increased Methylation of Interleukin 6 Gene Is Associated with Obesity in Korean Women. Mol Cells 2015; 38(5): 452–456
| Files | ||
| Issue | Vol 56, No 7 (2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Cytokine Inflammation Epigenetics MSP-PCR Single nucleotide polymorphism | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
