Association of two polymorphisms Asp299Gly and Thr399Ile in Toll-like receptor 4 with rheumatoid arthritis: A meta-analysis.

Publisher: Wiley on behalf of the Asia Pacific League of Associations for Rheumatology Country of Publication: England NLM ID: 101474930 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1756-185X (Electronic) Linking ISSN: 17561841 NLM ISO Abbreviation: Int J Rheum Dis Subsets: MEDLINE

Original Publication: [Oxford, UK] : Wiley on behalf of the Asia Pacific League of Associations for Rheumatology

Polymorphism, Single Nucleotide*; Arthritis, Rheumatoid/*genetics ; Toll-Like Receptor 4/*genetics; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/ethnology ; Arthritis, Rheumatoid/immunology ; Asian People/genetics ; Case-Control Studies ; China/epidemiology ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Phenotype ; Protective Factors ; Risk Assessment ; Risk Factors ; Spain/epidemiology ; Tunisia/epidemiology ; White People/genetics

Our meta-analysis aims to evaluate the association of Asp299Gly and Thr399Ile with rheumatoid arthritis (RA) susceptibility and severity. By manually searching 3 electronic databases (PubMed, Embase and Web of Science), relevant articles were collected. After checking eligibility for every study, this meta-analysis on eligible studies was performed under 5 genetic models: (1) allelic contrast; (2) heterozygous model; (3) homozygous model; (4) dominant model; (5) recessive model. In Spanish populations, a significantly decreased RA risk was identified in allelic comparison (odds ratio [OR] = 0.73, 95% CI 0.55 ~ 0.96) and dominant model (OR = 0.74, 95% CI 0.56 ~ 0.99) of Asp299Gly polymorphism. A trend of reduced risk was also observed under the heterozygous model (OR = 0.77, 95% CI 0.58 ~ 1.03). As for Thr399Ile, it might also have a protective effect on Spanish populations in allelic comparison (OR = 0.71, 95% CI 0.44 ~ 1.15). In contrast, for both Asp299Gly and Thr399Ile, a higher risk of RA was detected in Chinese Han populations. The frequency of both Asp299Gly and Thr399Ile increased in rheumatoid factor (RF)-positive subjects in Chinese patients (Asp299Gly, RF+:RF- = 0.165:0.145; Thr399Ile, RF+:RF- = 0.170:0.161) and decreased in Spanish patients (Asp299Gly, RF+:RF- = 0.060:0.073; Thr399Ile, RF+:RF- = 0.046:0.056), but not to a statistically significant extent. Our meta-analysis suggested that both Asp299Gly and Thr399Ile might have a protective effect on Spanish populations, but the 2 polymorphisms could act as a susceptible factor in Chinese Han populations. To confirm our results, further investigation concerning the functional impacts of Asp299Gly and Thr399Ile are still needed.
(© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Davis JM 3rd, Matteson EL, American College of R, European League Against R. My treatment approach to rheumatoid arthritis. Mayo Clin Proc. 2012;87(7):659-673.
Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003;423(6937):356-361.
MacGregor AJ, Snieder H, Rigby AS, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 2000;43(1):30-37.
Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987;30(11):1205-1213.
Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol. 2001;2(8):675-680.
Schroder NW, Schumann RR. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis. 2005;5(3):156-164.
Candore G, Colonna-Romano G, Balistreri CR, et al. Biology of longevity: role of the innate immune system. Rejuvenation Res. 2006;9(1):143-148.
Turner MW, Hamvas RMJ. Mannose-binding lectin: structure, function, genetics and disease associations. Rev Immunogenet. 2000;2(3):305-322.
Arbour NC, Lorenz E, Schutte BC, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000;25(2):187-191.
van der Graaf C, Kullberg BJ, Joosten L, et al. Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism. Cytokine. 2005;30(5):264-268.
Browning BL, Huebner C, Petermann I, et al. Has toll-like receptor 4 been prematurely dismissed as an inflammatory bowel disease gene? Association study combined with meta-analysis shows strong evidence for association. Am J Gastroenterol. 2007;102(11):2504-2512.
Snelgrove T, Lim S, Greenwood C, et al. Association of toll-like receptor 4 variants and ankylosing spondylitis: a case-control study. J Rheumatol. 2007;34(2):368-370.
Sanchez E, Orozco G, Lopez-Nevot MA, Jimenez-Alonso J, Martin J. Polymorphisms of toll-like receptor 2 and 4 genes in rheumatoid arthritis and systemic lupus erythematosus. Tissue Antigens. 2004;63(1):54-57.
Kilding R, Akil M, Till S, et al. A biologically important single nucleotide polymorphism within the toll-like receptor-4 gene is not associated with rheumatoid arthritis. Clin Exp Rheumatol. 2003;21(3):340-342.
Radstake TR, Franke B, Hanssen S, et al. The Toll-like receptor 4 Asp299Gly functional variant is associated with decreased rheumatoid arthritis disease susceptibility but does not influence disease severity and/or outcome. Arthritis Rheum. 2004;50(3):999-1001.
Wang Y, Chen L, Li F, et al. TLR4 rs41426344 increases susceptibility of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population. Pediatr Rheumatol Online J. 2017;15(1):12.
Lin YC, Chang YM, Yu JM, Yen JH, Chang JG, Hu CJ. Toll-like receptor 4 gene C119A but not Asp299Gly polymorphism is associated with ischemic stroke among ethnic Chinese in Taiwan. Atherosclerosis. 2005;180(2):305-309.
Zheng B, Li Q, Wei C, et al. Lack of association of TLR4 gene Asp299Gly and Thr399Ile polymorphisms with rheumatoid arthritis in Chinese Han population of Yunnan Province. Rheumatol Int. 2010;30(9):1249-1252.
Tizaoui K, Naouali A, Kaabachi W, Hamzaoui A, Hamzaoui K. Association of Toll like receptor Asp299Gly with rheumatoid arthritis risk: a systematic review of case-control studies and meta-analysis. Pathol Res Pract. 2015;211(3):219-225.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264-269, W64.
Guo J, Jin M, Zhang M, Chen K. A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies. PLoS One. 2012;7(1):e30585.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-1558.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-188.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088-1101.
Sellers RM, Payne JB, Yu F, LeVan TD, Walker C, Mikuls TR. TLR4 Asp299Gly polymorphism may be protective against chronic periodontitis. J Periodontal Res. 2016;51(2):203-211.
Yang H, Wei C, Li Q, et al. Association of TLR4 gene non-missense single nucleotide polymorphisms with rheumatoid arthritis in Chinese Han population. Rheumatol Int. 2013;33(5):1283-1288.
Garcia-Bermudez M, Lopez-Mejias R, Gonzalez-Juanatey C, et al. Lack of association between TLR4 rs4986790 polymorphism and risk of cardiovascular disease in patients with rheumatoid arthritis. DNA Cell Biol. 2012;31(7):1214-1220.
Kang ES, Lee J. Genotypic analysis of Asp299Gly and Thr399Ile polymorphism of Toll-like receptor 4 in systemic autoimmune diseases of Korean population. Rheumatol Int. 2007;27(9):887-889.
Lee YH, Bae SC, Kim JH, Song GG. Toll-like receptor polymorphisms and rheumatoid arthritis: a systematic review. Rheumatol Int. 2014;34(1):111-116.
Orozco G, Santana SM, Gonzalez-Gay M, González CI. Toll-like receptor 4 Asp299Gly polymorphism and rheumatoid arthrits: a replicative study in three different populations. Inmunolgia. 2005;24:205-207.
Gebura K, Swierkot J, Wysoczanska B, et al. Polymorphisms within genes involved in regulation of the NF-kappaB pathway in patients with rheumatoid arthritis. Int J Mol Sci. 2017;18(7):1432.
Emonts M, Hazes MJ, Houwing-Duistermaat JJ, et al. Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study. BMC Med Genet. 2011;12:36.
Alvarez-Rodriguez L, Lopez-Hoyos M, Beares I, et al. Toll-like receptor 4 gene polymorphisms in polymyalgia rheumatica and elderly-onset rheumatoid arthritis. Clin Exp Rheumatol. 2011;29(5):795-800.
Dhaouadi T, Sfar I, Haouami Y, et al. Polymorphisms of Toll-like receptor-4 and CD14 in systemic lupus erythematosus and rheumatoid arthritis. Biomark Res. 2013;1(1):20.
Sheedy FJ, The M. Mal/TIRAP S180L and TLR4 G299D polymorphisms are not associated with susceptibility to, or severity of, rheumatoid arthritis. Ann Rheum Dis. 2007;67:1328-1331.
Jaen O, Petit-Teixeira E, Kirsten H, et al. No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis. Arthritis Res Ther. 2009;11(1):R5.
Marinou I, Healy J, Mewar D, et al. Association of interleukin-6 and interleukin-10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody status. Arthritis Rheum. 2007;56(8):2549-2556.
Amital H, Rewald E, Levy Y, et al. Fibrosis regression induced by intravenous gammaglobulin treatment. Ann Rheum Dis. 2003;62(2):175-177.
Masi AT. Subcommittee for Scleroderma Criteria of the American Rheumatism Asoociation Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980;23:581-590.
LeRoy ECBC, Fleischmajer R, Jablonska S. Scleroderma (systemic sclerosis): classification, subset and pathogenesis. J Rheumatol. 1988;15:202-205.
Steen VD, Medsger TA Jr, Rodnan GP. D-Penicillamine therapy in progressive systemic sclerosis (scleroderma): a retrospective analysis. Ann Intern Med. 1982;97(5):652-659.
Clements PJ, Lachenbruch PA, Seibold JR, et al. Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol. 1993;20(11):1892-1896.

Keywords: meta-analysis; polymorphism; rheumatoid arthritis; single nucleotide polymorphisms

0 (TLR4 protein, human)
0 (Toll-Like Receptor 4)

Date Created: 20200620 Date Completed: 20210927 Latest Revision: 20221207

20240829

10.1111/1756-185X.13890

32558389