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The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms

  • Genes and Disease
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Abstract

Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible studies. Then, a comprehensive meta-analysis was performed by comparing PF+-SSc and PF−-SSc patients to identify genetic polymorphisms associated with the status of PF in SSc. Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis, IRF5 rs2004640 polymorphism (OR 1.12; 95% CI 1.02–1.22, P = 1.39 × 10−2), STAT4 rs7574865 polymorphism (OR 1.25; 95% CI 1.07–1.47, P = 5.3 × 10−3), IRAK1 rs1059702 polymorphism (OR 1.20; 95% CI 1.05–1.37, P = 0.007), and CTGF G-945C polymorphism (OR 1.42; 95% CI 1.18–1.71, P = 0.002) are associated with PF status in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5 rs10488631 polymorphisms are not. Since IRF5, STAT4, and IRAK1 are important regulatory factors in the control of innate immune responses and CTGF is involved in the synthesis of extracellular matrix, these results suggest a role of the innate immunity and matrix compounds in the pathogenesis of PF in SSc.

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Abbreviations

SSc:

Systemic sclerosis

PF:

Pulmonary fibrosis

STAT4:

Signal transducer and activator of transcription 4

SLE:

Systemic lupus erythematosus

TNFAIP3:

Tumor necrosis factor a -1 induced protein 3

CD226:

Cluster of differentiation 226

CD247:

Cluster of differentiation 247

IRF5:

Interferon regulatory factor 5

CTGF:

Connective tissue growth factor (CTGF)

IRAK1:

Interleukin-1 receptor-associated kinase 1

ECM:

Extracellular matrix

NLRP1:

NLR family, pyrin domain containing 1

PLCL2:

Phospholipase C like 2

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81371325), the Deutsche Forschungsgemeinschaft Ri1056-11/1-2, GRK1727 ‘‘Modulation of Autoimmunity’’, Eppenauer Foundation, and German Center for Lung Research (DZL).

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Authors and Affiliations

  1. Xiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiang’an Nan Rd., Xiamen, 361102, China

    Wenjie Zhao, Kuai Liu, Junfeng Zheng, Runda Huang, Jun Zou & Xinhua Yu

  2. Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Parkallee 22, 23845, Borstel, Germany

    Xiaoyang Yue, Gabriela Riemekasten, Frank Petersen & Xinhua Yu

  3. Department of Rheumatology, University of Lübeck, Ratzeburger allee 160, 23538, Lübeck, Germany

    Gabriela Riemekasten

  4. Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany

    Gabriela Riemekasten

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  1. Wenjie Zhao
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  2. Xiaoyang Yue
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  4. Junfeng Zheng
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  9. Xinhua Yu
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Correspondence to Xinhua Yu.

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Zhao, W., Yue, X., Liu, K. et al. The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms. Rheumatol Int 37, 1303–1310 (2017). https://doi.org/10.1007/s00296-017-3722-5

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  • DOI: https://doi.org/10.1007/s00296-017-3722-5

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