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The effect of TGF-β1 polymorphism on systemic sclerosis: a systematic review and pooled analysis of available literature

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Abstract

Transforming growth factor-β1 (TGF-β1) plays an important role in the pathogenesis of systemic sclerosis (SSc). To investigate whether TGF-β1 gene promoter polymorphisms were associated with the susceptibility of SSc, we performed a meta-analysis based on all available studies through PubMed, Elsevier Science Direct, Embase, and Chinese Biomedical, China National Knowledge Infrastructure and Google Scholar with the last report up to March 15, 2013. Crude odds ratios with 95 % confidence intervals were used to estimate the strength of the association. A fixed or random effects model was adopted according to heterogeneity test. Heterogeneity among studies was evaluated using I 2. Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Begg’s and Egger’s test. Totally, seven papers with 663 SSc patients and 908 healthy controls were subjected to the final analysis. These studies encompass seven for TGF-β1 codon 10, three for codon 25 and three for −509C/T. We failed to detect any association of these promoter polymorphism with SSc susceptibility. For TGF-β1 codon 10 polymorphism, subgroup analyses by race, genotype testing method and classification of SSc were further performed. Similarly, no association was observed. Significant heterogeneity was detected among the studies in all genetic models of TGF-β1 codon 10 polymorphism. Publication bias was absent. Taken together, our meta-analysis did not provided an evidence of confirming association between TGF-β1 (codon 10, codon 25, −509C/T) gene polymorphism and SSc. Nevertheless, due to smaller sample sizes, larger sample studies including different ethnic groups should be considered in future to confirm our results.

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References

  1. Nietert PJ, Silver RM (2000) Systemic sclerosis: environmental and occupational risk factors. Curr Opin Rheumatol 12:520–526

    Article  PubMed  CAS  Google Scholar 

  2. Scaletti C, Vultaggio A, Maqqi E et al (2001) Microchimerism and systemic sclerosis. Int Arch Allergy Immunol 125(3):196–202

    Article  PubMed  CAS  Google Scholar 

  3. Coral-Alvarado P, Pardo AL, Castano-Rodriguez N et al (2009) Systemic sclerosis: a world wide global analysis. Clin Rheumatol 28(7):757–765

    Article  PubMed  Google Scholar 

  4. Valentini G, Black C (2002) Systemic sclerosis. Best Pract Res Clin Rheumatol 16(5):807–816

    Article  PubMed  Google Scholar 

  5. Gilliam AC (2008) Scleroderma. Curr Dir Autoimmun. Basel, Karger 10: 258–279

  6. Fonseca C, Lindahl GE, Ponticos M et al (2007) A polymorphism in the CTGF promoter region associated with systemic sclerosis. N Enql J Med 357(12):1210–1220

    Article  CAS  Google Scholar 

  7. Ates O, Musellim B, Ongen G et al (2008) Analysis of TNF polymorphisms in Turkish systemic sclerosis patients with interstitial lung involvement. Biochem Genet 46(11–12):696–701

    Article  PubMed  CAS  Google Scholar 

  8. Mattuzzi S, Barbi S, Carletto A et al (2007) Association of polymorphisms in the IL1B and IL2 genes with susceptibility and severity of systemic sclerosis. J Rheumatol 34(5):997–1004

    PubMed  CAS  Google Scholar 

  9. Sato S, Haseqawa M, Takehara K (2001) Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis. J Dermatol Sci 27(2):140–146

    Article  PubMed  CAS  Google Scholar 

  10. Fujii D, Brissenden JE, Derynck R et al (1986) Transforming growth factor-b gene maps to human chromosome 19 long arm and to mouse chromosome 7. Somat Cell Mol Genet 12:281–288

    Article  PubMed  CAS  Google Scholar 

  11. Kim S, Glick A, Sporn MB et al (1989) Characterization of the promoter region of the human transforming growth factor-β1 gene. J Biol Chem 264:402–408

    PubMed  CAS  Google Scholar 

  12. Awad MR, El-Gamel A, Hasleton P et al (1998) Genotypic variation in the transforming growth factor-β1 gene: association with TGF-β1 production, fibrotic lung disease and graft fibrosis after lung transplantation. Transplantation 66:1014–1020

    Article  PubMed  CAS  Google Scholar 

  13. Massague J (1990) The transforming growth factor-beta family. Annu Rev Cell Biol 6:597–641

    Article  PubMed  CAS  Google Scholar 

  14. Granel B, Bernard F, Chevillard C (2009) Genetic susceptibility to systemic sclerosis from clinical aspect to genetic factor analyses. Eur J Intern Med 20(3):242–252

    Article  PubMed  CAS  Google Scholar 

  15. Leask A, Abraham DJ (2004) TGF-beta signaling and the fibrotic response. FASEB J 18(7):816–827

    Article  PubMed  CAS  Google Scholar 

  16. Beretta L, Cappiello F, Moore JH et al (2008) Ability of epistatic interactions of cytokine single-nucleotide polymorphisms to predict susceptibility to disease subsets in systemic sclerosis patients. Arthr Rheum 59(7):974–983

    Article  CAS  Google Scholar 

  17. Büyük U, Ates O, Dalyan L et al (2010) Analysis of transforming growth factor beta 1(TGF-beta1) gene polymorphisms in Turkish patients with scleroderma. Cell Biochem Funct 28(4):274–277

    Article  PubMed  Google Scholar 

  18. Crilly A, Hamilton J, Clark CJ et al (2002) Analysis of transforming growth factor beta1 gene polymorphisms in patients with systemic sclerosis. Ann Rheum Dis 61(8):678–681

    Article  PubMed  CAS  Google Scholar 

  19. Lee EB, Kim JY, Lee YJ et al (2004) Transforming growth factor-beta1 polymorphisms in Korean patients with systemic sclerosis. Tissue Antigens 63(5):491–495

    Article  PubMed  CAS  Google Scholar 

  20. Ohtsuka T, Yamakage A, Yamazaki S (2002) The polymorphism of transforming growth factor-β1 gene in Japanese patients with systemic sclerosis. Br J Dermatol 147(3):458–463

    Article  PubMed  CAS  Google Scholar 

  21. Suqiura Y, Banno S, Matsumoto Y et al (2003) Transforming growth factor beta 1 gene polymorphism in patients with systemic sclerosis. J Rheumatol 30(7):1520–1523

    Google Scholar 

  22. Zhou X, Tan FK, Stivers DN et al (2000) Microsatellites and intragenic polymorphisms of transforming growth factor beta and platelet-derived growth factor and their receptor genes in Native Americans with systemic sclerosis (scleroderma): a preliminary analysis showing no genetic association. Arthr Rheum 43(5):1068–1073

    Article  CAS  Google Scholar 

  23. Thakkinstian A, D’Este C, Eisman J et al (2004) Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study. J Bone Miner Res 19(3):419–428

    Article  PubMed  CAS  Google Scholar 

  24. Banerjee I (2010) Relationship between Paraoxonase 1 (PON1) gene polymorphisms and susceptibility of stroke: a meta-analysis. Eur J Epidemiol 25(7):449–458

    Article  PubMed  CAS  Google Scholar 

  25. Rahimi RA, Leof EB (2007) TGF-beta signaling: a tale of two responses. J Cell Biochem 102:593–608

    Article  PubMed  CAS  Google Scholar 

  26. Hatton N, Frech T, Smith B et al (2011) Transforming growth factor signalling: a common pathway in pulmonary arterial hypertension and systemic sclerosis. Int J Clin Pract Suppl 172:35–43

    Article  PubMed  Google Scholar 

  27. Ihn H (2008) Autocrine TGF-beta signaling in the pathogenesis of systemic sclerosis. J Dermatol Sci 49:103–113

    Article  PubMed  CAS  Google Scholar 

  28. Bhattacharyya S, Wei J, Tourtellotte WG et al (2012) Fibrosis in systemic sclerosis: common and unique pathobiology. Fibrogenesis Tissue Repair 5(Suppl 1):S18

    Article  PubMed  Google Scholar 

  29. Varga J (2002) Scleroderma and Smads: dysfunctional Smad family dynamics culminating in fibrosis. Arthr Rheum 46:1703–1713

    Article  CAS  Google Scholar 

  30. Whitfield ML, Finlay DR, Murray JI et al (2003) Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci USA 100:12319–12324

    Article  PubMed  CAS  Google Scholar 

  31. Pandey JP, LeRoy EC (2002) A profibrotic polymorphism (of TGF beta1) in systemic sclerosis. Ann Rheum Dis 61(8):671–672

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partly supported by grants from the Natural Science foundation of Anhui Province (Code: 1308085MH169), and the Key Project of the Education Department of Anhui Province Natural Science Research (Code: KJ2012A165).

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No conflict of interest had been declared by the authors.

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Correspondence to Jing Wang.

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Ya-nan Wan and Yu-jie Wang contributed equally to this work and should be considered co-first authors.

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Wan, Yn., Wang, Yj., Yan, Jw. et al. The effect of TGF-β1 polymorphism on systemic sclerosis: a systematic review and pooled analysis of available literature. Rheumatol Int 33, 2859–2865 (2013). https://doi.org/10.1007/s00296-013-2826-9

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  • DOI: https://doi.org/10.1007/s00296-013-2826-9

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