Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
July-2014 Volume 8 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2014 Volume 8 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population

  • Authors:
    • Hua Zeng
    • Haiyan Yan
    • Zhixian Zhang
    • Weizhen Fang
    • Rui Ding
    • Lisi Huang
    • Mei Chen
    • Jin Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China, Department of Endocrinology, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China
  • Pages: 213-218
    |
    Published online on: May 12, 2014
       https://doi.org/10.3892/etm.2014.1707
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Interleukin‑21 (IL‑21) is a pleiotropic cytokine linking innate and adaptive immune responses, which has been reported to play a key role in multiple autoimmune diseases. The aim of the present case‑control study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of rs907715 within the IL‑21 gene and Graves' disease (GD) in a Southern Chinese population. A total of 211 patients with GD and 212 control subjects were recruited for the study. IL‑21 gene rs907715 polymorphisms were detected by direct DNA sequencing. The results indicated that the frequencies of the GG genotype and the G allele in GD patients were significantly increased when compared with the frequencies in the controls (P=6.7x10‑3 and P=2.0x10‑5, respectively). In addition, the frequency of the AA genotype was much lower in the patient group when compared with the control group (16.6 vs. 34.0%; P=4.0x10‑5). Furthermore, the G allele of rs907715 was associated with relapse in GD patients. These observations indicated that polymorphisms of IL‑21/rs907715 may affect the susceptibility to GD in a Southern Chinese population. The G allele was significantly associated with an increased risk of GD development, whereas the A allele may lower the susceptibility to GD.
View Figures

Figure 1

View References

1 

Di Paola R, Menzaghi C, De Filippis V, Corda D and Di Cerbo A: Cyclooxygenase-dependent thyroid cell proliferation induced by immunoglobulins from patients with Graves’ disease. J Clin Endocrinol Metab. 82:670–673. 1997.PubMed/NCBI

2 

Chistiakov DA: Thyroid-stimulating hormone receptor and its role in Graves’ disease. Mol Genet Metab. 80:377–388. 2003.

3 

Weetman AP: Graves’ disease. N Engl J Med. 343:1236–1248. 2000.

4 

Farid NR and Balazs C: The genetics of thyroid associated ophthalmopathy. Thyroid. 8:407–409. 1998. View Article : Google Scholar

5 

Falgarone G, Heshmati HM, Cohen R and Reach G: Mechanisms in endocrinology. Role of emotional stress in the pathophysiology of Graves’ disease. Eur J Endocrinol. 168:R13–R18. 2012.PubMed/NCBI

6 

Jacobson EM and Tomer Y: The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future. J Autoimmun. 28:85–98. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Brand OJ, Barrett JC, Simmonds MJ, et al: Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves’ disease. Hum Mol Genet. 18:1704–1713. 2009.

8 

Jia HY, Zhang ZG, Gu XJ, et al: Association between interleukin 21 and Graves’ disease. Genet Mol Res. 10:3338–3346. 2011.

9 

Simmonds MJ, Howson JM, Heward JM, et al: A novel and major association of HLA-C in Graves’ disease that eclipses the classical HLA-DRB1 effect. Hum Mol Genet. 16:2149–2153. 2007.PubMed/NCBI

10 

Simmonds MJ, Howson JM, Heward JM, et al: Regression mapping of association between the human leukocyte antigen region and Graves disease. Am J Hum Genet. 76:157–163. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Heward JM, Brand OJ, Barrett JC, et al: Association of PTPN22 haplotypes with Graves’ disease. J Clin Endocrinol Metab. 92:685–690. 2007.

12 

Vaidya B, Imrie H, Perros P, et al: The cytotoxic T lymphocyte antigen-4 is a major Graves’ disease locus. Hum Mol Genet. 8:1195–1199. 1999.PubMed/NCBI

13 

Ban Y, Tozaki T, Taniyama M, Tomita M and Ban Y: Association of a CTLA-4 3′ untranslated region (CT60) single nucleotide polymorphism with autoimmune thyroid disease in the Japanese population. Autoimmunity. 38:151–153. 2005.

14 

Ettinger R, Kuchen S and Lipsky PE: Interleukin 21 as a target of intervention in autoimmune disease. Ann Rheum Dis. 67(Suppl 3): iii83–iii86. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Spolski R and Leonard WJ: Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol. 26:57–79. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Habib T, Senadheera S, Weinberg K and Kaushansky K: The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3. Biochemistry. 41:8725–8731. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Caruso R, Fina D, Peluso I, et al: A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells. Gastroenterology. 132:166–175. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Jüngel A, Distler JH, Kurowska-Stolarska M, et al: Expression of interleukin-21 receptor, but not interleukin-21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis. Arthritis Rheum. 50:1468–1476. 2004.

19 

Distler JH, Jüngel A, Kowal-Bielecka O, et al: Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis. Arthritis Rheum. 52:856–864. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Davis ID, Skak K, Smyth MJ, et al: Interleukin-21 signaling: functions in cancer and autoimmunity. Clin Cancer Res. 13:6926–6932. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Li Y, Bleakley M and Yee C: IL-21 influences the frequency, phenotype, and affinity of the antigen-specific CD8 T cell response. J Immunol. 175:2261–2269. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Parrish-Novak J, Dillon SR, Nelson A, et al: Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 408:57–63. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Zeng R, Spolski R, Finkelstein SE, et al: Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J Exp Med. 201:139–148. 2005.PubMed/NCBI

24 

Ozaki K, Spolski R, Ettinger R, et al: Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol. 173:5361–5371. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Ettinger R, Sims GP, Fairhurst AM, et al: IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. J Immunol. 175:7867–7879. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Ozaki K, Spolski R, Feng CG, et al: A critical role for IL-21 in regulating immunoglobulin production. Science. 298:1630–1634. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Sawalha AH, Kaufman KM, Kelly JA, et al: Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus. Ann Rheum Dis. 67:458–461. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Li J, Shen W, Kong K and Liu Z: Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis. Scand J Immunol. 64:515–522. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Coenen MJ and Gregersen PK: Rheumatoid arthritis: a view of the current genetic landscape. Genes Immun. 10:101–111. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Asano K, Ikegami H, Fujisawa T, et al: Molecular scanning of interleukin-21 gene and genetic susceptibility to type 1 diabetes. Hum Immunol. 68:384–391. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Zhang J, Zeng H, Ren M, et al: Interleukin-21 is associated with disease activity in patients with Graves’ disease. Endocrine. Nov 28–2013.(Epub ahead of print).

32 

Meller J, Jauho A, Hüfner M, Gratz S and Becker W: Disseminated thyroid autonomy or Graves’ disease: reevaluation by a second generation TSH receptor antibody assay. Thyroid. 10:1073–1079. 2000.

33 

Liu L, Wu HQ, Wang Q, Zhu YF, et al: Association between thyroid stimulating hormone receptor gene intron polymorphisms and autoimmune thyroid disease in a Chinese Han population. Endocr J. 59:717–723. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Simmonds MJ, Heward JM, Carr-Smith J, et al: Contribution of single nucleotide polymorphisms within FCRL3 and MAP3K7IP2 to the pathogenesis of Graves’ disease. J Clin Endocrinol Metab. 91:1056–1061. 2006.PubMed/NCBI

35 

Plagnol V, Howson JM, Smyth DJ, et al: Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet. 7:e10022162011. View Article : Google Scholar : PubMed/NCBI

36 

Festen EA, Goyette P, Scott R, et al: Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis. Gut. 58:799–804. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Zeng R, Spolski R, Casas E, et al: The molecular basis of IL-21-mediated proliferation. Blood. 109:4135–4142. 2007. View Article : Google Scholar : PubMed/NCBI

38 

Konforte D and Paige CJ: Identification of cellular intermediates and molecular pathways induced by IL-21 in human B cells. J Immunol. 177:8381–8392. 2006. View Article : Google Scholar : PubMed/NCBI

39 

Coquet JM, Kyparissoudis K, Pellicci DG, et al: IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production. J Immunol. 178:2827–2834. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Rahman M, Nara H, Onoda T, et al: Cloning and characterization of an isoform of interleukin-21. FEBS Lett. 581:4001–4009. 2007. View Article : Google Scholar : PubMed/NCBI

41 

King C, Ilic A, Koelsch K and Sarvetnick N: Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell. 117:265–277. 2004. View Article : Google Scholar : PubMed/NCBI

42 

Monteleone G, Monteleone I, Fina D, et al: Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn’s disease. Gastroenterology. 128:687–694. 2005.PubMed/NCBI

43 

di Carlo E, de Totero D, Piazza T, Fabbi M and Ferrini S: Role of IL-21 in immune-regulation and tumor immunotherapy. Cancer Immunol Immunother. 56:1323–1334. 2007.PubMed/NCBI

44 

Ding L, Wang S, Chen GM, et al: A single nucleotide polymorphism of IL-21 gene is associated with systemic lupus erythematosus in a Chinese population. Inflammation. 35:1781–1785. 2012. View Article : Google Scholar : PubMed/NCBI

45 

Liu Y, Helms C, Liao W, et al: A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet. 4:e10000412008. View Article : Google Scholar

46 

Leonard WJ and Spolski R: Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol. 5:688–698. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zeng H, Yan H, Zhang Z, Fang W, Ding R, Huang L, Chen M and Zhang J: Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population. Exp Ther Med 8: 213-218, 2014.
APA
Zeng, H., Yan, H., Zhang, Z., Fang, W., Ding, R., Huang, L. ... Zhang, J. (2014). Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population. Experimental and Therapeutic Medicine, 8, 213-218. https://doi.org/10.3892/etm.2014.1707
MLA
Zeng, H., Yan, H., Zhang, Z., Fang, W., Ding, R., Huang, L., Chen, M., Zhang, J."Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population". Experimental and Therapeutic Medicine 8.1 (2014): 213-218.
Chicago
Zeng, H., Yan, H., Zhang, Z., Fang, W., Ding, R., Huang, L., Chen, M., Zhang, J."Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population". Experimental and Therapeutic Medicine 8, no. 1 (2014): 213-218. https://doi.org/10.3892/etm.2014.1707
Copy and paste a formatted citation
x
Spandidos Publications style
Zeng H, Yan H, Zhang Z, Fang W, Ding R, Huang L, Chen M and Zhang J: Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population. Exp Ther Med 8: 213-218, 2014.
APA
Zeng, H., Yan, H., Zhang, Z., Fang, W., Ding, R., Huang, L. ... Zhang, J. (2014). Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population. Experimental and Therapeutic Medicine, 8, 213-218. https://doi.org/10.3892/etm.2014.1707
MLA
Zeng, H., Yan, H., Zhang, Z., Fang, W., Ding, R., Huang, L., Chen, M., Zhang, J."Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population". Experimental and Therapeutic Medicine 8.1 (2014): 213-218.
Chicago
Zeng, H., Yan, H., Zhang, Z., Fang, W., Ding, R., Huang, L., Chen, M., Zhang, J."Association between IL‑21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population". Experimental and Therapeutic Medicine 8, no. 1 (2014): 213-218. https://doi.org/10.3892/etm.2014.1707
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team