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The association between G-197A gene polymorphism of IL-17A with changes in protein interaction of IL-17A, levels of urinary IL-17, and degree of lupus nephritis abnormality

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Abstract

Elevated levels of IL-17 in systemic lupus erythematosus (SLE) patients have been reported to be correlated to renal disorders, but the involvement of the G-197A gene polymorphism of IL 17 in lupus nephritis (LN) and the degree of renal abnormality have not been reported. Therefore, the aim of this study was to investigate these associations. This study involved 30 LN patients and 20 healthy control. Levels of uIL-17 were measured by ELISA, while the G-197A gene polymorphisms of IL-17A were examined using polymerase chain reaction (PCR) and sequence analysis. Changes in the protein structure due to G-197A gene polymorphism of IL-17A were analyzed by in silico investigation. In addition, renal biopsies were performed to determine the degree of renal abnormality (classes I–VI). A significant difference was found between LN patients and the control group in term of uIL-17 levels (p = 0.004). However, the G-197A gene polymorphism of IL-17A between LN patients and the control group were not significantly different (p = 0.154). There were no difference in the levels of uIL-17 between patients and control group on G-197A gene polymorphism of IL-17A (p = 0.682). Also, there were no significant differences in G-197A gene polymorphism of IL-17A toward the degree of nephritis (p = 0.300). In silico investigation showed that G197A gene polymorphism of IL-17A resulted in changes of the pattern of IRF-4 binding to the promoter, thereby affecting its activity. In conclusion, the levels of uIL-17 in LN patients were significantly higher than those in the control group, but G-197A gene polymorphism of IL-17A did not cause varying levels of IL-17 and did not influence the degree of renal abnormalities in LN.

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Abbreviations

LN:

Lupus nephritis

SLE:

Systemic lupus erythematosus

IL:

Interleukin

GVHD:

Graft-versus-host disease

ACR:

American College of Rheumatology

ELISA:

Enzyme link immunosorbent assay

PCR:

Polymerase chain reaction

OR:

Odds ratio

NFAT:

Nuclear factor of activated T cells

MPO:

Myeloperoxidase

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Acknowledgments

We would like to thank the Director of Saiful Anwar Hospital and the Dean of Brawijaya University faculty of medicine, Malang, Indonesia, for providing the grant and to all of those involved in this research.

Authors’ contribution

AG wrote the manuscript and performed the renal biopsies. HS participated in the study design and revised the manuscript. EI and SF participated in the study. NW performed bioinformatic analyses. KH, AG, and HK edited the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, Brawijaya University Faculty of Medicine/Dr. Saiful Anwar Hospital Malang, Malang, East Java, Indonesia

    Atma Gunawan & Handono Kalim

  2. Department of Clinical Pathology, Brawijaya University Faculty of Medicine/Dr. Saiful Anwar Hospital Malang, Malang, East Java, Indonesia

    Hani Susianti, Eky Indyanty, Siti Fatonah & Kusworini Handono

  3. Department of Biology, Brawijaya University Faculty of Science, Malang, East Java, Indonesia

    Nashi Widodo

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  1. Atma Gunawan
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Correspondence to Atma Gunawan.

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The authors declare that they have no competing interests.

Human rights statements and informed consent

All procedures followed were by the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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Gunawan, A., Susianti, H., Indyanty, E. et al. The association between G-197A gene polymorphism of IL-17A with changes in protein interaction of IL-17A, levels of urinary IL-17, and degree of lupus nephritis abnormality. Comp Clin Pathol 25, 535–541 (2016). https://doi.org/10.1007/s00580-016-2222-4

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  • DOI: https://doi.org/10.1007/s00580-016-2222-4

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