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Association between circulating transforming growth factor-β1 level and polymorphisms in systemic lupus erythematosus and rheumatoid arthritis: A meta-analysis
Corresponding Author(s) : Y. H. Lee
Cellular and Molecular Biology,
Vol. 63 No. 1: Issue 1
Abstract
This study systemically reviewed evidence regarding the relationship between circulating blood transforming growth factor-β1 (TGF-β1) levels and systemic lupus erythematous (SLE) and rheumatoid arthritis (RA), and associations between TGF-β1 polymorphisms and susceptibility to SLE and RA. We conducted a meta-analysis on the serum/plasma TGF-β1 levels in SLE and RA patients and healthy controls, and the associations between TGF-β1 +869 T/C, +915 C/G, and -509 T/C polymorphisms and SLE or RA risk. Twenty-eight studies were considered in this meta-analysis. Circulating TGF-β1 levels were significantly lower in the SLE group than in controls (SMD = -1.164, 95% CI = -2.257 – -0.070, P = 0.037). Serum/plasma TGF-β1 levels were not significantly different between RA and control groups (SMD = 0.699, 95% CI = -0.379 – 1.717, p = 0.211). No association between TGF-β1 +869 T/C polymorphism and SLE was found. However, meta-analysis showed an association between the TGF-β1 +869 T allele and RA in all subjects (OR = 1.282, 95% CI = 1.118–1.470, P = 3.8 x 10-4). Analysis after stratification by ethnicity indicated that the T allele was significantly associated with RA in Asians and Arabs (OR = 1.429, 95% CI = 1.179–1.733, P = 2.9 x 10-4; OR = 1.352, 95% CI = 1.097–1.668, P = 0.005), but not Europeans. However, no association was found between TGF-β1 +915 G/C or -509 C/T polymorphisms and RA or SLE. Meta-analysis revealed a significantly lower circulating TGF-β1 level in SLE patients, and a significant association between TGF-β1 +869 T/C polymorphism and RA development.
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- Ruiz-Irastorza G, Khamashta MA, Castellino G,Hughes GR. Systemic lupus erythematosus. Lancet 2001; 357: 1027-1032.
- Mellado M, Martínez-Muñoz L, Cascio G, Lucas P, Pablos JL,Rodríguez-Frade JM. T cell migration in rheumatoid arthritis. Frontiers in immunology 2015; 6.
- Letterio JJ,Roberts AB. Regulation of immune responses by TGF-β*. Annual review of immunology 1998; 16: 137-161.
- Aoki CA, Borchers AT, Li M, et al. Transforming growth factor β (TGF-β) and autoimmunity. Autoimmunity reviews 2005; 4: 450-459.
- Ohtsuka K, Gray J, Stimmler M,Horwitz D. The relationship between defects in lymphocyte production of transforming growth factor-β1 in systemic lupus erythematosus and disease activity or severity. Lupus 1999; 8: 90-94.
- Chu C-Q, Field M, Abney E, et al. Transforming growth factor"β1 in rheumatoid synovial membrane and cartilage pannus junction. Clinical & Experimental Immunology 1991; 86: 380-386.
- Zhang L, Yan J-w, Wang Y-X, et al. Association of TGF-β1+ 869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis. Molecular biology reports 2013; 40: 4811-4817.
- Yamada Y, Miyauchi A, Goto J, et al. Association of a Polymorphism of the Transforming Growth Factor"β1 Gene with Genetic Susceptibility to Osteoporosis in Postmenopausal Japanese Women. Journal of Bone and Mineral Research 1998; 13: 1569-1576.
- Awad M, El-Gamel A, Hasleton P, Turner D, Sinnott P,Hutchinson I. Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation 1998; 66: 1014-1020.
- Grainger DJ, Heathcote K, Chiano M, et al. Genetic control of the circulating concentration of transforming growth factor type β1. Human molecular genetics 1999; 8: 93-97.
- Sayed SK, Galal SH, Herdan OM,Mahran AM. Single nucleotide polymorphism T869C of transforming growth factor-beta 1 gene and systemic lupus erythematosus: association with disease susceptibility and lupus nephritis. Egypt J Immunol 2014; 21: 9-21.
- Antiga E, Del Bianco E, Difonzo E, Fabbri P,Caproni M. Serum levels of the regulatory cytokines transforming growth factor-beta and interleukin-10 are reduced in patients with discoid lupus erythematosus. Lupus 2011; 20: 556-560.
- Becker-Merok A, Eilertsen Gí˜,Nossent JC. Levels of transforming growth factor-β are low in systemic lupus erythematosus patients with active disease. The Journal of rheumatology 2010; 37: 2039-2045.
- Hammad AM, Youssef HM,El-Arman MM. Transforming growth factor beta 1 in children with systemic lupus erythematosus: a possible relation with clinical presentation of lupus nephritis. Lupus 2006; 15: 608-612.
- Lu LY, Cheng HH, Sung PK, Yeh JJ, Shiue YL,Chen A. Single-nucleotide polymorphisms of transforming growth factor-beta1 gene in Taiwanese patients with systemic lupus erythematosus. J Microbiol Immunol Infect 2004; 37: 145-152.
- Bennett AL, Chao CC, Hu S, et al. Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome. J Clin Immunol 1997; 17: 160-166.
- Harman H, Tekeoglu I, Gurol G, et al. Comparison of fetuin-A and transforming growth factor beta 1 levels in patients with spondyloarthropathies and rheumatoid arthritis. Int J Rheum Dis 2016.
- Mieliauskaite D, Venalis P, Dumalakiene I, Venalis A,Distler J. Relationship between serum levels of TGF-beta1 and clinical parameters in patients with rheumatoid arthritis and Sjogren's syndrome secondary to rheumatoid arthritis. Autoimmunity 2009; 42: 356-358.
- Rico MC, Manns JM, Driban JB, Uknis AB, Kunapuli SP,Cadena RAD. Thrombospondin-1 and transforming growth factor beta are pro-inflammatory molecules in rheumatoid arthritis. Translational Research 2008; 152: 95-98.
- Eriksson P, Andersson C, Ekerfelt C, Ernerudh J,Skogh T. Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjogren's syndrome, rheumatoid arthritis and healthy controls. Clin Exp Immunol 2004; 137: 617-620.
- Rezaei A, Ziaee V, Sharabian FT, et al. Lack of association between interleukin-10, transforming growth factor-beta gene polymorphisms and juvenile-onset systemic lupus erythematosus. Clin Rheumatol 2015; 34: 1059-1064.
- Wang B, Morinobu A, Kanagawa S, et al. Transforming growth factor beta 1 gene polymorphism in Japanese patients with systemic lupus erythematosus. Kobe J Med Sci 2007; 53: 15-23.
- Guarnizo"Zuccardi P, Lopez Y, Giraldo M, et al. Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue antigens 2007; 70: 376-382.
- Caserta TM, Knisley AA, Tan FK, Arnett FC,Brown TL. Genotypic analysis of the TGF beta-509 allele in patients with systemic lupus erythematosus and Sjogren's syndrome. Ann Genet 2004; 47: 359-363.
- Schotte H, Willeke P, Rust S, et al. The transforming growth factor-beta1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus. Lupus 2003; 12: 86-92.
- Saad MN, Mabrouk MS, Eldeib AM,Shaker OG. Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis. PLoS One 2015; 10: e0131960.
- Hussein YM, Mohamed RH, El-Shahawy EE,Alzahrani SS. Interaction between TGF-beta1 (869C/T) polymorphism and biochemical risk factor for prediction of disease progression in rheumatoid arthritis. Gene 2014; 536: 393-397.
- Zhou TB, Zhao HL, Fang SL,Drummen GP. Association of transforming growth factor-beta1 T869C, G915C, and C509T gene polymorphisms with rheumatoid arthritis risk. J Recept Signal Transduct Res 2014; 34: 469-475.
- Lee YH, Woo JH, Choi SJ, Ji JD,Song GG. Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus: An International Journal 2010; 19: 703-710.
- Lee YH, Woo JH, Choi SJ, Ji JD,Song GG. Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis. Lupus: An International Journal 2009; 18: 9-15.
- Lee YH, Woo JH, Choi SJ, Ji JD,Song GG. Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Molecular biology reports 2010; 37: 227-234.
- Moher D, Liberati A, Tetzlaff J, Altman DG,Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097.
- Hozo SP, Djulbegovic B,Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC medical research methodology 2005; 5: 13.
- Ridout KK, Ridout SJ, Price LH, Sen S,Tyrka AR. Depression and telomere length: A meta-analysis. Journal of affective disorders 2016; 191: 237-247.
- Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd edn. Hillsdale, New Jersey: L. Erlbaum, 1988.
- Egger M, Smith GD,Phillips AN. Meta-analysis: principles and procedures. BMJ 1997; 315: 1533-1537.
- DerSimonian R,Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188.
- Higgins JP,Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558.
- Egger M, Davey Smith G, Schneider M,Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634.
- Taylor A, Verhagen J, Blaser K, Akdis M,Akdis CA. Mechanisms of immune suppression by interleukin"10 and transforming growth factor"β: the role of T regulatory cells. Immunology 2006; 117: 433-442.
- Gualtierotti R, Biggioggero M, Penatti A,Meroni P. Updating on the pathogenesis of systemic lupus erythematosus. Autoimmunity reviews 2010; 10: 3-7.
- Filippi CM, Juedes AE, Oldham JE, et al. Transforming Growth Factor-β Suppresses the Activation of CD8+ T-Cells When Naí¯ve but Promotes Their Survival and Function Once Antigen Experienced A Two-Faced Impact on Autoimmunity. Diabetes 2008; 57: 2684-2692.
- Zhou T-B, Zhao H-L, Fang S-L,Drummen GP. Association of transforming growth factor-β1 T869C, G915C, and C509T gene polymorphisms with rheumatoid arthritis risk. Journal of Receptors and Signal Transduction 2014; 34: 469-475.
References
Ruiz-Irastorza G, Khamashta MA, Castellino G,Hughes GR. Systemic lupus erythematosus. Lancet 2001; 357: 1027-1032.
Mellado M, Martínez-Muñoz L, Cascio G, Lucas P, Pablos JL,Rodríguez-Frade JM. T cell migration in rheumatoid arthritis. Frontiers in immunology 2015; 6.
Letterio JJ,Roberts AB. Regulation of immune responses by TGF-β*. Annual review of immunology 1998; 16: 137-161.
Aoki CA, Borchers AT, Li M, et al. Transforming growth factor β (TGF-β) and autoimmunity. Autoimmunity reviews 2005; 4: 450-459.
Ohtsuka K, Gray J, Stimmler M,Horwitz D. The relationship between defects in lymphocyte production of transforming growth factor-β1 in systemic lupus erythematosus and disease activity or severity. Lupus 1999; 8: 90-94.
Chu C-Q, Field M, Abney E, et al. Transforming growth factor"β1 in rheumatoid synovial membrane and cartilage pannus junction. Clinical & Experimental Immunology 1991; 86: 380-386.
Zhang L, Yan J-w, Wang Y-X, et al. Association of TGF-β1+ 869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis. Molecular biology reports 2013; 40: 4811-4817.
Yamada Y, Miyauchi A, Goto J, et al. Association of a Polymorphism of the Transforming Growth Factor"β1 Gene with Genetic Susceptibility to Osteoporosis in Postmenopausal Japanese Women. Journal of Bone and Mineral Research 1998; 13: 1569-1576.
Awad M, El-Gamel A, Hasleton P, Turner D, Sinnott P,Hutchinson I. Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation 1998; 66: 1014-1020.
Grainger DJ, Heathcote K, Chiano M, et al. Genetic control of the circulating concentration of transforming growth factor type β1. Human molecular genetics 1999; 8: 93-97.
Sayed SK, Galal SH, Herdan OM,Mahran AM. Single nucleotide polymorphism T869C of transforming growth factor-beta 1 gene and systemic lupus erythematosus: association with disease susceptibility and lupus nephritis. Egypt J Immunol 2014; 21: 9-21.
Antiga E, Del Bianco E, Difonzo E, Fabbri P,Caproni M. Serum levels of the regulatory cytokines transforming growth factor-beta and interleukin-10 are reduced in patients with discoid lupus erythematosus. Lupus 2011; 20: 556-560.
Becker-Merok A, Eilertsen Gí˜,Nossent JC. Levels of transforming growth factor-β are low in systemic lupus erythematosus patients with active disease. The Journal of rheumatology 2010; 37: 2039-2045.
Hammad AM, Youssef HM,El-Arman MM. Transforming growth factor beta 1 in children with systemic lupus erythematosus: a possible relation with clinical presentation of lupus nephritis. Lupus 2006; 15: 608-612.
Lu LY, Cheng HH, Sung PK, Yeh JJ, Shiue YL,Chen A. Single-nucleotide polymorphisms of transforming growth factor-beta1 gene in Taiwanese patients with systemic lupus erythematosus. J Microbiol Immunol Infect 2004; 37: 145-152.
Bennett AL, Chao CC, Hu S, et al. Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome. J Clin Immunol 1997; 17: 160-166.
Harman H, Tekeoglu I, Gurol G, et al. Comparison of fetuin-A and transforming growth factor beta 1 levels in patients with spondyloarthropathies and rheumatoid arthritis. Int J Rheum Dis 2016.
Mieliauskaite D, Venalis P, Dumalakiene I, Venalis A,Distler J. Relationship between serum levels of TGF-beta1 and clinical parameters in patients with rheumatoid arthritis and Sjogren's syndrome secondary to rheumatoid arthritis. Autoimmunity 2009; 42: 356-358.
Rico MC, Manns JM, Driban JB, Uknis AB, Kunapuli SP,Cadena RAD. Thrombospondin-1 and transforming growth factor beta are pro-inflammatory molecules in rheumatoid arthritis. Translational Research 2008; 152: 95-98.
Eriksson P, Andersson C, Ekerfelt C, Ernerudh J,Skogh T. Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjogren's syndrome, rheumatoid arthritis and healthy controls. Clin Exp Immunol 2004; 137: 617-620.
Rezaei A, Ziaee V, Sharabian FT, et al. Lack of association between interleukin-10, transforming growth factor-beta gene polymorphisms and juvenile-onset systemic lupus erythematosus. Clin Rheumatol 2015; 34: 1059-1064.
Wang B, Morinobu A, Kanagawa S, et al. Transforming growth factor beta 1 gene polymorphism in Japanese patients with systemic lupus erythematosus. Kobe J Med Sci 2007; 53: 15-23.
Guarnizo"Zuccardi P, Lopez Y, Giraldo M, et al. Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue antigens 2007; 70: 376-382.
Caserta TM, Knisley AA, Tan FK, Arnett FC,Brown TL. Genotypic analysis of the TGF beta-509 allele in patients with systemic lupus erythematosus and Sjogren's syndrome. Ann Genet 2004; 47: 359-363.
Schotte H, Willeke P, Rust S, et al. The transforming growth factor-beta1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus. Lupus 2003; 12: 86-92.
Saad MN, Mabrouk MS, Eldeib AM,Shaker OG. Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis. PLoS One 2015; 10: e0131960.
Hussein YM, Mohamed RH, El-Shahawy EE,Alzahrani SS. Interaction between TGF-beta1 (869C/T) polymorphism and biochemical risk factor for prediction of disease progression in rheumatoid arthritis. Gene 2014; 536: 393-397.
Zhou TB, Zhao HL, Fang SL,Drummen GP. Association of transforming growth factor-beta1 T869C, G915C, and C509T gene polymorphisms with rheumatoid arthritis risk. J Recept Signal Transduct Res 2014; 34: 469-475.
Lee YH, Woo JH, Choi SJ, Ji JD,Song GG. Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus: An International Journal 2010; 19: 703-710.
Lee YH, Woo JH, Choi SJ, Ji JD,Song GG. Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis. Lupus: An International Journal 2009; 18: 9-15.
Lee YH, Woo JH, Choi SJ, Ji JD,Song GG. Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Molecular biology reports 2010; 37: 227-234.
Moher D, Liberati A, Tetzlaff J, Altman DG,Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097.
Hozo SP, Djulbegovic B,Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC medical research methodology 2005; 5: 13.
Ridout KK, Ridout SJ, Price LH, Sen S,Tyrka AR. Depression and telomere length: A meta-analysis. Journal of affective disorders 2016; 191: 237-247.
Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd edn. Hillsdale, New Jersey: L. Erlbaum, 1988.
Egger M, Smith GD,Phillips AN. Meta-analysis: principles and procedures. BMJ 1997; 315: 1533-1537.
DerSimonian R,Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188.
Higgins JP,Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558.
Egger M, Davey Smith G, Schneider M,Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634.
Taylor A, Verhagen J, Blaser K, Akdis M,Akdis CA. Mechanisms of immune suppression by interleukin"10 and transforming growth factor"β: the role of T regulatory cells. Immunology 2006; 117: 433-442.
Gualtierotti R, Biggioggero M, Penatti A,Meroni P. Updating on the pathogenesis of systemic lupus erythematosus. Autoimmunity reviews 2010; 10: 3-7.
Filippi CM, Juedes AE, Oldham JE, et al. Transforming Growth Factor-β Suppresses the Activation of CD8+ T-Cells When Naí¯ve but Promotes Their Survival and Function Once Antigen Experienced A Two-Faced Impact on Autoimmunity. Diabetes 2008; 57: 2684-2692.
Zhou T-B, Zhao H-L, Fang S-L,Drummen GP. Association of transforming growth factor-β1 T869C, G915C, and C509T gene polymorphisms with rheumatoid arthritis risk. Journal of Receptors and Signal Transduction 2014; 34: 469-475.