TGFB1 (rs1800470 and rs1800469) variants are independently associated with disease activity and autoantibodies in rheumatoid arthritis patients.
1,800,469
Genetic variants
Rheumatoid arthritis
Transforming growth factor-β1
rs1800470
Journal
Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
16
10
2020
accepted:
13
05
2021
pubmed:
29
5
2021
medline:
25
2
2022
entrez:
28
5
2021
Statut:
ppublish
Résumé
To evaluate the association between TGFB1 + 869 T > C (rs1800470) and TGFB1-509 C > T (rs1800469) variants with susceptibility for rheumatoid arthritis (RA), disease activity, presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and TGF-β1 plasma levels. A total of 262 patients with RA and 168 control individuals were tested for the TGFB1 variants using a TaqMan genotyping assay. Disease activity score in 28 joints (DAS28) classified RA patients into two groups of disease activity: remission/mild (DAS28 < 3.2) and moderate/severe (DAS28 ≥ 3.2). TGFB1 + 869 T > C and -509 C > T variants, independently or in haplotype combination, were not associated with RA's susceptibility. Patients with the TGFB1-509 TT genotype had a higher frequency of DAS28 ≥ 3.2 (OR 2.58, 95% CI 1.04-6.42, p = 0.041). The TGFB1 + 869 CC genotype in seropositive patients for RF or anti-CCP was associated with decreased TGF-β1 levels (p = 0.032 and p = 0.039, respectively). Patients with the TGFB1 + 869 C allele and elevated RF titles demonstrated a higher frequency of DAS28 ≥ 3.2 (p = 0.037). The TGFB1 + 869 T > C variant was associated with diminished TGF-β1 plasma levels and moderate/severe activity disease only in seropositive RF patients. This is the first study showing that TGF-β1 plasma levels can be modulated by the interaction between the TGFB1 + 869 T > C variant and autoantibodies. However, the TGFB1-509 C > T variant was associated with moderate/severe activity disease, independently of autoantibodies positivity. Thus, our findings suggest that TGFB1 + 869 T > C and -509 C > T variants can predict activity disease in different RA patient subgroups.
Identifiants
pubmed: 34046752
doi: 10.1007/s10238-021-00725-9
pii: 10.1007/s10238-021-00725-9
doi:
Substances chimiques
Autoantibodies
0
TGFB1 protein, human
0
Transforming Growth Factor beta1
0
Rheumatoid Factor
9009-79-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
37-45Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Mateen S, Zafar A, Moin S, Khan AQ, Zubair S. Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clin Chim Acta. 2016;455:161–71.
pubmed: 26883280
Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018;6(1):15.
pubmed: 5920070
pmcid: 5920070
Malmström V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nat Rev Immunol. 2017;17(1):60–75.
pubmed: 27916980
pmcid: 27916980
Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors: clinical applications. Dis Markers. 2013;35(6):727–34.
pubmed: 24324289
pmcid: 3845430
Rantapää-Dahlqvist S, de Jong BAW, Berglin E, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003;48(10):2741–9.
pubmed: 14558078
pmcid: 14558078
Sokolove J, Zhao X, Chandra PE, Robinson WH. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγ receptor. Arthritis Rheum. 2011;63(1):53–62.
pubmed: 20954191
pmcid: 20954191
Niu Q, Cai B, Huang Z, Shi Y, Wang L. Disturbed Th17/Treg balance in patients with rheumatoid arthritis. Rheumatol Int. 2012;32(9):2731–6.
pubmed: 21809006
Wang X, Yang C, Xu F, Qi L, Wang J, Yang P. Imbalance of circulating Tfr/Tfh ratio in patients with rheumatoid arthritis. Clin Exp Med. 2019;19(1):55–64.
pubmed: 30284646
Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. 2005;6(4):345–52.
pubmed: 15785760
Zheng SG, Wang J, Wang P, Gray JD, Horwitz DA. IL-2 Is essential for TGF-β to convert naive CD4 + CD25 − Cells to CD25 + Foxp3 + regulatory T CELLS AND FOR EXPANSION OF THESE CELLS. J Immunol. 2007;178(4):2018–27.
pubmed: 17277105
Li MO, Wan YY, Sanjabi S, Robertson A-KL, Flavell RA. Transforming growth factor-β regulation of immune responses. Annu Rev Immunol. 2006;24(1):99–146.
pubmed: 16551245
Paradowska-Gorycka A, Trefler J, Maciejewska-Stelmach J, Łącki JK. Interleukin-10 gene promoter polymorphism in Polish rheumatoid arthritis patients. Int J Immunogenet. 2010;37(4):225–31.
pubmed: 20477882
de Medeiros FA, Alfieri DF, Iriyoda TMV, et al. TNF-β +252 A>G (rs909253) polymorphism is independently associated with presence of autoantibodies in rheumatoid arthritis patients. Clin Exp Med. 2019;19(3):347–56.
pubmed: 31049794
Zhou T-B, Zhao H-L, Fang S-L, Drummen GPC. Association of transforming growth factor-β1 T869C, G915C, and C509T gene polymorphisms with rheumatoid arthritis risk. J Recept Signal Transduct. 2014;34(6):469–75.
Lee YH, Bae S-C. Association between circulating transforming growth factor-β1 level and polymorphisms in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis. Cell Mol Biol (Noisy-le-grand). 2017;63(1):53–9.
Yamada Y, Okuizumi H, Miyauchi A, Takagi Y, Ikeda K, Harada A. Association of transforming growth factor β1 genotype with spinal osteophytosis in Japanese women. Arthritis Rheum. 2000;43(2):452.
pubmed: 10693888
Hussein YM, Mohamed RH, El-Shahawy EE, Alzahrani SS. Interaction between TGF-β1 (869C/T) polymorphism and biochemical risk factor for prediction of disease progression in rheumatoid arthritis. Gene. 2014;536(2):393–7.
pubmed: 24315820
Shah R, Rahaman B, Hurley CK, Posch PE. Allelic diversity in the TGFB1 regulatory region: characterization of novel functional single nucleotide polymorphisms. Hum Genet. 2006;119(1–2):61–74.
pubmed: 16369764
Cao H, Zhou Q, Lan R, et al. A Functional Polymorphism C-509T in TGFβ-1 Promoter Contributes to Susceptibility and Prognosis of Lone Atrial Fibrillation in Chinese Population. Jeyaseelan K, ed. PLoS One. 2014; 9(11):e112912.
Guo W, Dong Z, Guo Y, et al. Polymorphisms of transforming growth factor-β1 associated with increased risk of gastric cardia adenocarcinoma in north China. Int J Immunogenet. 2011;38(3):215–24.
pubmed: 21205231
Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81.
Anderson J, Caplan L, Yazdany J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken). 2012;64(5):640–7.
Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928–9.
pubmed: 16720584
de Paz B, Alperi-López M, Ballina-García FJ, Prado C, Gutiérrez C, Suárez A. Cytokines and regulatory T cells in rheumatoid arthritis and their relationship with response to corticosteroids. J Rheumatol. 2010;37(12):2502–10.
pubmed: 20952465
Hashemi V, Farrokhi AS, Tanomand A, et al. Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and disease activity in patients with rheumatoid arthritis in Iranian population. Immunol Lett. 2018;204:16–22.
pubmed: 30292536
Sanjabi S, Oh SA, Li MO. Regulation of the immune response by TGF-β: from conception to autoimmunity and infection. Cold Spring Harb Perspect Biol. 2017;9(6):a022236.
pubmed: 28108486
pmcid: 5453394
Chen D-Y, Chen Y-M, Chen H-H, Hsieh C-W, Lin C, Lan J-L. The associations of circulating CD4 + CD25 high regulatory T cells and TGF-β with disease activity and clinical course in patients with adult-onset Still’s disease. Connect Tissue Res. 2010;51(5):370–7.
pubmed: 20388015
Jin T, Almehed K, Carlsten H, Forsblad-d’Elia H. Decreased serum levels of TGF-β1 are associated with renal damage in female patients with systemic lupus erythematosus. Lupus. 2012;21(3):310–8.
pubmed: 22072025
Zhang L, Yan J, Wang Y-X, et al. Association of TGF-β1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis. Mol Biol Rep. 2013;40(8):4811–7.
pubmed: 23645040
Kobayashi T, Murasawa A, Ito S, et al. Cytokine gene polymorphisms associated with rheumatoid arthritis and periodontitis in Japanese adults. J Periodontol. 2009;80(5):792–9.
pubmed: 19405833
Alayli G, Kara N, Tander B, Canturk F, Gunes S, Bagci H. Association of transforming growth factor β1 gene polymorphism with rheumatoid arthritis in a Turkish population. Jt Bone Spine. 2009;76(1):20–3.
Panoulas VF, Douglas KMJ, Smith JP, et al. Transforming growth factor- 1 869T/C, but not interleukin-6 -174G/C, polymorphism associates with hypertension in rheumatoid arthritis. Rheumatology. 2008;48(2):113–8.
pubmed: 19106168
Pokorny V. Transforming growth factor 1 gene (HSTGFB1) nucleotide T869C (codon 10) polymorphism is not associated with prevalence or severity of rheumatoid arthritis in a Caucasian population. Ann Rheum Dis. 2003;62(9):907–8.
pubmed: 12922971
pmcid: 1754668
Kim S, Han S, Kim G, Lee J, Kang Y. TGF-ß1 polymorphism determines the progression of joint damage in rheumatoid arthritis. Scand J Rheumatol. 2004;33(6):389–94.
pubmed: 15794197
Patel SL, Prakash J, Gupta V. TGF-β1 +869C/T polymorphism increases susceptibility to rheumatoid arthritis in North Indian population. Clin Rheumatol. 2020;39(10):2881–8.
pubmed: 32270333
Sugiura Y. Transforming growth factor beta1 gene polymorphism in rheumatoid arthritis. Ann Rheum Dis. 2002;61(9):826–8.
pubmed: 12176809
pmcid: 1754235
Saad MN, Mabrouk MS, Eldeib AM, Shaker OG. Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis. Garcia de Frutos P, ed. PLoS One. 2015; 10(7):e0131960.
Sun W, Yi M, Bai Y, et al. Correlations between the polymorphism of +869T/C in TGF-β1 and rheumatoid arthritis. J Musculoskelet Neuronal Interact. 2019;19(1):127–32.
pubmed: 30839312
pmcid: 6454251
Yamamoto K, Okada Y, Suzuki A, Kochi Y. Genetics of rheumatoid arthritis in Asia–present and future. Nat Rev Rheumatol. 2015;11(6):375–9.
pubmed: 25668139
Ceccarelli F, Perricone C, Fabris M, et al. Transforming growth factor β 869C/T and interleukin 6–174G/C polymorphisms relate to the severity and progression of bone-erosive damage detected by ultrasound in rheumatoid arthritis. Arthritis Res Ther. 2011;13(4):R111.
pubmed: 21740541
pmcid: 3239349
Coutant F. Pathogenic effects of anti-citrullinated protein antibodies in rheumatoid arthritis – role for glycosylation. Jt Bone Spine. 2019;86(5):562–7.
Scherer HU, van der Woude D, Ioan-Facsinay A, et al. Glycan profiling of anti-citrullinated protein antibodies isolated from human serum and synovial fluid. Arthritis Rheum. 2010;62(6):1620–9.
pubmed: 20178128
pmcid: 20178128
Reparon-Schuijt CC, van Esch WJE, van Kooten C, et al. Secretion of anti-citrulline-containing peptide antibody by B lymphocytes in rheumatoid arthritis. Arthritis Rheum. 2001;44(1):41–7.
pubmed: 11212174
Innala L, Kokkonen H, Eriksson C, Jidell E, Berglin E, Dahlqvst SR. Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides. J Rheumatol. 2008;35(6):1002–8.
pubmed: 18398946
Chen Y, Dawes PT, Packham JC, Mattey DL. Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther. 2012;14(2):R81.
pubmed: 22513132
pmcid: 3446455
Welsing PMJ, Landewé RBM, Van Riel PLCM, et al. The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis. Arthritis Rheum. 2004;50(7):2082–93.
pubmed: 15248205
Kavanaugh A, Fleischmann RM, Emery P, et al. Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann Rheum Dis. 2013;72(1):64–71.
pubmed: 22562973
Smolen JS, Van Der Heijde DMFM, St.Clair EW, , et al. Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum. 2006;54(3):702–10.
pubmed: 16508926
Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492–509.
pubmed: 24161836
Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3–15.
pubmed: 25969430
Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000;275(24):18138–44.
pubmed: 10747905
Martelossi Cebinelli GC, Paiva Trugilo K, Badaró Garcia S, Brajão de Oliveira K. TGF-β1 functional polymorphisms: a review. Eur Cytokine Netw. 2016;27(4):81–9.
pubmed: 28396298