Abstract
Rheumatoid arthritis (RA) is a chronic, systemic disease of unknown etiology. Several studies have reported a variable number of tandem repeat (VNTR) 86 bp (rs2234663) in the intron 2 of IL1RN gene with RA risk. The present study was designed to determine the frequencies of this polymorphism in patients with RA and control subjects (CS) and its association with RA in a western Mexican population. An analytical cross-sectional study was performed, in which 350 patients with RA and 307 CS were included. The identification of IL1RN VNTR polymorphism was carried out by polymerase chain reaction (PCR), and genotypes were associated with clinical variables (DAS28 and CRP). The presence of A1/A2 genotype was associated with RA risk (p = 0.03, OR = 1.45, 95% CI = 1.02–2.05). Also, results indicate that the presence of heterozygote genotypes which include A2 was associated with RA risk (p = 0.01, OR = 1.5, 95% CI = 1.07–2.11). Patients carrier of A2/A2 genotype have a higher score of DAS28 (5.64 [4.49–6.70]). A-/A- has higher level of CRP (2.30 [0.62–9.10]) in comparison with A2/A- (1.06 [0.37–2.82]). A1/A2 genotype was associated with susceptibility to RA in a western Mexican population. The presence of the A2/A2 genotype in RA is associated with increased disease activity.
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Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet 388:2023–2038
Jalil SF, Arshad M, Bhatti A et al (2016) Rheumatoid arthritis: what have we learned about the causing factors? Pak J Pharm Sci 29:629–645
Ali A, Mohamed Thoufic M, Vino S (2016) Genetic markers as therapeutic target in rheumatoid arthritis: a game changer in clinical therapy? Rheumatol Int 36:1601–1607
Carreira PE, Gonzalez-Crespo MR, Ciruelo E et al (2005) Polymorphism of the interleukin-1 receptor antagonist gene: a factor in susceptibility to rheumatoid arthritis in a Spanish population. Arthritis Rheum 52:3015–3019
Swellam M, Abu Gabal KM, Youssef SS (2013) Interleukin-1 receptor antagonist gene polymorphism and hepcidin in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. IUBMB Life 65:883–888
Satoh T, Otsuka A, Contassot E et al (2015) The inflammasome and IL-1β: implications for the treatment of inflammatory diseases. Immunotherapy 7:243–254
Fragoso JM, Delgadillo H, Llorente L et al (2010) Interleukin 1 receptor antagonist polymorphisms are associated with the risk of developing acute coronary syndrome in Mexicans. Immunol Lett 133:106–111
López MES, Ávila RG, Hernández E et al (2013) The interleukin-1 gene cluster polymorphisms are associated with Takayasu’s arteritis in Mexican patients. J Interf Cytokine Res 33:369–375
Pérez-Suárez TG, Gutiérrez-Robledo LM, Ávila-Funes JA et al (2016) VNTR polymorphisms of the IL-4 and IL-1RN genes and their relationship with frailty syndrome in Mexican community-dwelling elderly. Aging Clin Exp Res 28:823–832
Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69:1580–1588
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
Mansfield JC, Holden H, Tarlow JK et al (1994) Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology 106:637–642
Torres-Carrillo NM, Ruiz-Noa Y et al (2012) The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the western Mexico. Immunol Lett 147:41–46
Torres-Carrillo N, Ontiveros-Mercado H, Torres-Carrillo NM et al (2013) The -319C/+49G/CT60G haplotype of CTLA-4 gene confers susceptibility to rheumatoid arthritis in Mexican population. Cell Biochem Biophys 67:1217–1228
Guzmán-Guzmán IP, Reyes-Castillo Z, Muñoz-Barrios S et al (2015) Polymorphisms and functional haplotype in PADI4: further evidence for contribution on rheumatoid arthritis susceptibility and anti-cyclic citrullinated peptide antibodies in a western Mexican population. Immunol Lett 163:214–220
You C-g, Li J-f, Xie X-d et al (2007) Association of interleukin-1 genetic polymorphisms with the risk of rheumatoid arthritis in Chinese population. Clin Chem Lab Med 45:968–971
Lagha A, Zidi S, Stayoussef M et al (2015) Interleukin-1β, interleukin1-Ra, interleukin-10, and tumor necrosis factor-a polymorphisms in Tunisian patients with rheumatoid arthritis. Pathol Biol (Paris) 63:179–184
Allam I, Djidjik R, Ouikhlef N et al (2013) Interleukin-1 and the interleukin-1 receptor antagonist gene polymorphisms study in patients with rheumatoid arthritis. IUBMB Life 65:883–888
Arman A, Yilmaz B, Coker A et al (2006) Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1B gene polymorphisms in Turkish patients with rheumatoid arthritis. Clin Exp Rheumatol 24:643–648
Vargas-Alarcon G, Ramírez-Bello J, Juárez-Cedillo T et al (2012) Distribution of the IL-1RN, IL-6, IL-10, INF-γ, and TNF-A gene polymorphisms in the Mexican population. Genet Test Mol Biomarkers 16:1246–1253
Cvetkovic JT, Wallberg-Jonsson BS et al (2002) Susceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-alpha, IL-1beta, and IL-1Ra genes. J Rheumatol 29:212–219
Lubbe S, Tikly M, van der Merwe L et al (2008) Interleukin-1 receptor antagonist gene polymorphisms are associated with disease severity in black South Africans with rheumatoid arthritis. Joint Bone Spine 75:422–425
Ismail E, Nofal OKJ, Sakthiswary R et al (2016) The clinical significance of interleukin-1 receptor antagonist +2018 polymorphism in rheumatoid arthritis. PLoS One 11:e0153752
Fang F, Pan J, Li Y et al (2015) Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: a meta-analysis. Hum Immunol 76:1–5
Lee YH, Bae S-C (2015) Associations between interleukin-1 and IL-1 receptor antagonist polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. Cell Mol Biol 61:105–111
Tolusso B, Pietrapertosa D, Morelli A et al (2006) IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein plasma levels and response to therapy. Pharmacogenomics 7:683–695
Witkin SS, Gerber S, Ledger WJ (2002) Influence of interleukin-1 receptor antagonist gene polymorphism on disease. Clin Infect Dis 34:204–209
Berger P, McConnell JP, Nunn M et al (2002) C-reactive protein levels are influenced by common IL-1 gene variations. Cytokine 17:171–174
Latkovskis G, Licis N, Kalnins U (2004) C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease. Eur J Immunogenet 31:207–213
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This investigation was supported by Fondo Sectorial IMSS-ISSSTE-CONACYT. No. 161749.
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Ramírez-Pérez, S., Salazar-Páramo, M., Pineda-Monjarás, S. et al. Association of 86 bp variable number of tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL1RN) with susceptibility and clinical activity in rheumatoid arthritis. Clin Rheumatol 36, 1247–1252 (2017). https://doi.org/10.1007/s10067-017-3610-0
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DOI: https://doi.org/10.1007/s10067-017-3610-0