Fatma SILAN, Öztürk ÖZDEMİR, Çoşkun ZATERİ, Ayla AKBAL, Betül SARGIN, Yılmaz SAVAŞ, Hatice RESORLU

The frequency of toll-like receptor 4 gene polymorphism in ankylosing spondylitis and its relationship between disease activity

Objective. We aimed to evaluate the frequency of toll-like receptor 4 (TLR4) gene polymorphism and itsrelationship between disease activity in patients with ankylosing spondylitis (AS). Methods. Forty-one ASpatients (25 male/16 female) fullfilling the 1984 Modified New York Criteria and 41 healthy controls (25male/16 female) were included in this study. Disease activity of the AS patients was assesed by Bath AnkylosingSpondylitis Disease Activity Index (BASDAI). The TLR4 gene polymorphism of AS patients and healthycontrols were analyzed by Real-Time Polymerase Chain Reaction (PCR) System. Results. Three (7.3%) patientswith AS had TLR4 gene polymorphism compared with healthy controls (0/41; 0%). Two of these patients hadheterozygous mutation and one had homozygous mutation. Significant correlation was not found betweenTLR4 gene polymorphism and BASDAI score (p > 0.05). Conclusions. In our study, TLR4 gene polymorphismwas higher in patients with AS compared with control group. But, this polymorphism was not associated withdisease activity, erythrocyte sedimentation rate and C-reactive protein levels

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[1] Li Q, Li L, Bi L, Xiao C, Lin Z, Cao S, et al. Kunxian capsules in the treatment of patients with ankylosing spondylitis:a randomized placebo-controlled clinical trial. Trials 2016;17:337.
[2] Mahmoudi M, Aslani S, Nicknam MH, Karami J, Jamshidi AR. New insights toward the pathogenesis of ankylosing spondylitis; genetic variations and epigenetic modification. Mod Rheumatol 2017;27:198-209.
[3] Almasi S, Aslani S, Poormoghim H, Jamshidi AR, Poursani S, Mahmoudi M. Gene expression profiling of toll like receptor 4 and 5 in peripheral blood mononuclear cells in rheumatic disorders: ankylosing spondylitis and rheumatoid arthritis. Iran J Allergy Asthma Immunol 2016;15:87-92.
[4] Hansen IS, Hoepel W, Zaat SAJ, Baeten DLP, den Dunnen J. Serum IgA immune complexes promote proinflammatory cytokine production by human macrophages, monocytes, and Kupffer cells through FcαRI-TLR cross-talk. J Immunol 2017 Nov 8. pii: ji1700883. doi: 10.4049/jimmunol.1700883.
[5] Kratz A, Plebani M, Peng M, Lee YK, McCafferty R, Machin SJ; International Council for Standardization in Haematology (ICSH). ICSH recommendations for modified and alternate methods measuring the erythrocyte sedimentation rate. Int J Lab Hematol 2017;39:448-57.
[6] Hashemi R, Majidi A, Motamed H, Amini A, Najari F, Tabatabaey A. Erythrocyte sedimentation rate measurement using as a rapid alternative to the Westergren Method. Emerg (Tehran) 2015;3:50-3.
[7] Wacewicz M, Socha K,Soroczyńska J,Niczyporuk M, Aleksiejczuk P,Ostrowska J,et al. Concentration of selenium, zinc, copper, Cu/Zn ratio, total antioxidant status and c-reactive protein in the serum of patients with psoriasis treated by narrow-band ultraviolet B phototherapy: a case-control study. J Trace Elem Med Biol 2017;44:109-14.
[8] Pérez BC, Nieto AI, Torrente M, Jiménez SC, Calvo V, Gutierrez SL,et al. Comparison of methods for circulating cell-free DNA isolation using blood from cancer patients:impact on biomarker testing. Transl Lung Cancer Res 2016;5:665- 72.
[9] Romero-Sanchez C, Chila L, Gómez A, Casas MC, Bautista-Molano W, Briceño I, et al. The frequency of HLA-B27 in a Colombian population with signs of spondyloarthritis. Curr Rheumatol Rev 2017 Mar 29. doi: 10.2174/1573397113666170329121552.
[10] Marzia D, Elisa T, Andrea P, Giuseppe P, Francesca M, Claudio L, et al. Gene Expression analysis before and after treatment with adalimumab in patients with ankylosing spondylitis identifies molecular pathways associated with response to therapy. Genes (Basel) 2017;8:127.
[11] Akbal A, Oğuz S, Gökmen F, Bilim S, Reşorlu H, Sılan F, et al. C reactive protein gene and Toll-like receptor 4 gene polymorphisms can relate to the development of psoriatic arthritis. Clin Rheumatol 2015;34:301-6.
[12] Cheng L, Zhang Z, Li G, Li F, Wang L, Zhang L, et al. Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system. Vaccine 2017;35:6143-53.
[13] Gergely P Jr, Blazsek A, Weiszhar Z, Pazar B, Poor G. Lack of genetic association of the Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile polymorphisms with spondylarthropathies in a Hungarian population. Rheumatology (Oxford) 2006;45:1194-6.
[14] Pointon JJ, Chapman K, Harvey D, Sims AM, Bradbury L, Laiho K, et al Toll-like receptor 4 and CD14 polymorphisms in ankylosing spondylitis: evidence of a weak association in Finns. J Rheumatol 2008;35:1609-12.
[15] Xu WD, Liu SS, Pan HF, Ye DQ. Lack of association of TLR4 polymorphisms with susceptibility to rheumatoid arthritis and ankylosing spondylitis: a meta-analysis. Joint Bone Spine 2012;79:566-9.
[16] Na KS, Kim TH, Rahman P, Peddle L, Choi CB, Inman RD. Analysis of single nucleotide polymorphisms in Toll-like receptor 4 shows no association with ankylosing spondylitis in a Korean population. Rheumatol Int 2008;28:627- 30.
[17] Adam R, Sturrock RD, Gracie JA. TLR4 mutations (Asp299Gly and Thr399Ile) are not associated with ankylosing spondylitis. Ann Rheum Dis 2006;65:1099-101.
[18] van der Paardt M, Crusius JB, de Koning MH, Morré SA, van de Stadt RJ, Dijkmans BA, et al. No evidence for involvement of the Toll-like receptor 4 (TLR4) A896G and CD14-C260T polymorphisms in susceptibility to ankylosing spondylitis. Ann Rheum Dis 2005;64:235-8.
[19] Yang ZX, Liang Y, Zhu Y, Li C, Zhang LZ, Zeng XM, et al. Increased expression of Toll-like receptor 4 in peripheral blood leucocytes and serum levels of some cytokines in patients with ankylosing spondylitis. Clin Exp Immunol 2007;149:48-55.
[20] De Rycke L, Vandooren B, Kruithof E, De Keyser F, Veys EM, Baeten D. Tumor necrosis factor alpha blockade treatment down-modulates the increased systemic and local expression of Toll-like receptor 2 and Toll-like receptor 4 in spondylarthropathy. Arthritis Rheum 2005;52:2146-58.
[21] Snelgrove T, Lim S, Greenwood C, Peddle L, Hamilton S, Inman R, et al. Association of toll-like receptor 4 variants and ankylosing spondylitis: a casecontrol study. J Rheumatol 2007;34:368-70.
[22] Assassi S, Reveille JD, Arnett FC, Weisman MH, Ward MM, Agarwal SK, et al. Wholeblood gene expression profiling in ankylosing spondylitis shows upregulation of toll-like receptor 4 and 5. J Rheumatol 2011;38:87-98.