Skip to main content
SpringerLink
Log in

The −1123G>C Variant of PTPN22 Gene Promoter is Associated with Latent Autoimmune Diabetes in Adult Chinese Hans

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

The protein tyrosine phosphatase non-receptor 22 (PTPN22) gene encodes for lymphoid protein tyrosine phosphatase. Recent studies demonstrated the association between the +1858T, −1123G>C variants of PTPN22 gene and type 1 diabetes mellitus in Caucasian and Japanese populations. This study examined the relationship between the polymorphism of PTPN22 gene and latent autoimmune 1 diabetes in adults (LADA) in Chinese Hans. We studied 229 adult Chinese patients with LADA (LADA group) and 210 healthy volunteers (control group). The −1123G>C and +1858C>T polymorphisms of PTPN22 gene were determined by PCR-restriction fragment length polymorphism method. Further, genotypic/allelic frequencies and clinical characteristics were compared between two groups. There was a significant difference of frequencies of the −1123G>C polymorphism between LADA and control groups (OR = 1.99, 95% CI = 1.24–3.2; P = 0.001). However, no significant differences in the +1858C>T genotypic (CC, CT) and allelic (C, T) frequencies were found. Furthermore, the frequencies of the −1123 GC, CC genotype in male patients with LADA were significantly higher compared with male healthy volunteers (OR = 1.65, 95% CI = 1.21–2.26; P = 0.005). The analysis of covariance demonstrated no difference between glycosylated hemoglobin, body mass index, duration of diabetes, C-peptide, and GAD-Ab titer between the group carrying GC/CC and the group without allele C. In conclusion, the −1123G>C promoter polymorphism of PTPN22 gene, but not the +1858C>T variant, is associated with LADA in adult Chinese Hans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Knip, M., & Siljander, H. (2008). Autoimmune mechanisms in type 1 diabetes. Autoimmunity Reviews, 7, 550–557.

    Article  PubMed  CAS  Google Scholar 

  2. Liu, Y., Wenzlau, J. M., Yu, L., Patel, C., Eisenbarth, G. S., Hutton, J. C., et al. (2008). Conserved epitopes in the protein tyrosine phosphatase family of diabetes autoantigens. Annals of the New York Academy of Sciences, 1150, 245–247.

    Article  PubMed  CAS  Google Scholar 

  3. Gregersen, P. K. (2005). Gaining insight into PTPN22 and autoimmunity. Nature Genetics, 37, 1300–1302.

    Article  PubMed  CAS  Google Scholar 

  4. Hinks, A., Barton, A., John, S., Bruce, I., Hawkins, C., Griffiths, C. E., et al. (2005). Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Arthritis and Rheumatism, 52, 1694–1699.

    Article  PubMed  CAS  Google Scholar 

  5. Dieude, P., Teixeira, V. H., Pierlot, C., Cornelis, F., & Petit-Teixeira, E. (2008). Testing for linkage and association with rheumatoid arthritis a ptpn22 promoter polymorphism reported to be associated and linked with type 1 diabetes in the Caucasian population. Annals of the Rheumatic Diseases, 67, 900–901.

    Article  PubMed  CAS  Google Scholar 

  6. Dultz, G., Matheis, N., Dittmar, M., Rohrig, B., Bender, K., & Kahaly, G. J. (2009). The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes. Thyroid, 19, 143–148.

    Article  PubMed  CAS  Google Scholar 

  7. Bottini, N., Vang, T., Cucca, F., & Mustelin, T. (2006). Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Seminars in Immunology, 18, 207–213.

    Article  PubMed  CAS  Google Scholar 

  8. Zheng, W., & She, J. X. (2005). Genetic association between a lymphoid tyrosine phosphatase (PTPN22) and type 1 diabetes. Diabetes, 54, 906–908.

    Article  PubMed  CAS  Google Scholar 

  9. Onengut-Gumuscu, S., Ewens, K. G., Spielman, R. S., & Concannon, P. (2004). A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families. Genes and Immunity, 5, 678–680.

    Article  PubMed  CAS  Google Scholar 

  10. Chelala, C., Duchatelet, S., Joffret, M. L., Bergholdt, R., Dubois-Laforgue, D., Ghandil, P., et al. (2007). PTPN22 R620W functional variant in type 1 diabetes and autoimmunity related traits. Diabetes, 56, 522–526.

    Article  PubMed  CAS  Google Scholar 

  11. Zoledziewska, M., Perra, C., Orru, V., Moi, L., Frongia, P., Congia, M., et al. (2008). Further evidence of a primary, causal association of the PTPN22 620W variant with type 1 diabetes. Diabetes, 57, 229–234.

    Article  PubMed  CAS  Google Scholar 

  12. Hermann, R., Lipponen, K., Kiviniemi, M., Kakko, T., Veijola, R., Simell, O., et al. (2006). Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes. Diabetologia, 49, 1198–1208.

    Article  PubMed  CAS  Google Scholar 

  13. Santiago, J. L., Martinez, A., de la Calle, H., Fernandez-Arquero, M., Figueredo, M. A., de la Concha, E. G., et al. (2007). Susceptibility to type 1 diabetes conferred by the PTPN22 C1858T polymorphism in the Spanish population. BMC Medical Genetics, 8, 54.

    Article  PubMed  Google Scholar 

  14. Douroudis, K., Prans, E., Haller, K., Nemvalts, V., Rajasalu, T., Tillmann, V., et al. (2008). Protein tyrosine phosphatase non-receptor type 22 gene variants at position 1858 are associated with type 1 and type 2 diabetes in Estonian population. Tissue Antigens, 72, 425–430.

    Article  PubMed  CAS  Google Scholar 

  15. Saccucci, P., Del, D. E., Rapini, N., Verrotti, A., Piccinini, S., Maccari, A., et al. (2008). Association between PTPN22 C1858T and type 1 diabetes: a replication in continental Italy. Tissue Antigens, 71, 234–237.

    Article  PubMed  CAS  Google Scholar 

  16. Cinek, O., Hradsky, O., Ahmedov, G., Slavcev, A., Kolouskova, S., Kulich, M., et al. (2007). No independent role of the −1123G>C and +2740A>G variants in the association of PTPN22 with type 1 diabetes and juvenile idiopathic arthritis in two Caucasian populations. Diabetes Research and Clinical Practice, 76, 297–303.

    Article  PubMed  CAS  Google Scholar 

  17. Kawasaki, E., Awata, T., Ikegami, H., Kobayashi, T., Maruyama, T., Nakanishi, K., et al. (2006). Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): association between a promoter polymorphism and type 1 diabetes in Asian populations. American Journal of Medical Genetics, Part A, 140, 586–593.

    Article  Google Scholar 

  18. Baniasadi, V., & Das, S. N. (2008). No evidence for association of PTPN22 R620 W functional variant C1858T with type 1 diabetes in Asian Indians. Journal of Cellular and Molecular Medicine, 12, 1061–1062.

    Article  PubMed  CAS  Google Scholar 

  19. American Diabetes Association. (2011). Standards of medical care in diabetes–2011. Diabetes Care, 34(Suppl 1), S11–S61.

    Google Scholar 

  20. Petrone, A., Spoletini, M., Zampetti, S., Capizzi, M., Zavarella, S., Osborn, J., et al. (2008). The PTPN22 1858T gene variant in type 1 diabetes is associated with reduced residual beta-cell function and worse metabolic control. Diabetes Care, 31, 1214–1218.

    Article  PubMed  CAS  Google Scholar 

  21. Nielsen, C., Hansen, D., Husby, S., & Lillevang, S. T. (2007). Sex-specific association of the human PTPN22 1858T-allele with type 1 diabetes. International Journal of Immunogenetics, 34, 469–473.

    Article  PubMed  CAS  Google Scholar 

  22. Li, X., Yang, L., Zhou, Z., Huang, G., & Yan, X. (2003). Glutamic acid decarboxylase 65 autoantibody levels discriminate two subtypes of latent autoimmune diabetes in adults. Chinese Medical Journal (English Edition), 116, 1728–1732.

    CAS  Google Scholar 

  23. Petrone, A., Suraci, C., Capizzi, M., Giaccari, A., Bosi, E., Tiberti, C., et al. (2008). The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with high GAD antibody titer in latent autoimmune diabetes in adults: non insulin requiring autoimmune diabetes (NIRAD) Study 3. Diabetes Care, 31, 534–538.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Shanghai Health Bureau (grant no. 054012) and The National Natural Science Fund (81070650).

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Shanghai Jiaotong University, Affiliated Sixth People’s Hospital, Shanghai Clinical Center of Diabetes, Shanghai Institute for Diabetes, 600 Yishan Road, Shanghai, 200233, China

    Fang Liu, Jiang Liu, Tai-shan Zheng, Qing Li, Chen Wang, Xiao-ping Pan & Huijuan Lu

  2. Department of Neurology, Shanghai Jiaotong University, Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, China

    Yu-wu Zhao

Authors
  1. Fang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tai-shan Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiao-ping Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Huijuan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yu-wu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu-wu Zhao.

Additional information

Fang Liu and Jiang Liu contributed equally to this paper and should be considered as co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, F., Liu, J., Zheng, Ts. et al. The −1123G>C Variant of PTPN22 Gene Promoter is Associated with Latent Autoimmune Diabetes in Adult Chinese Hans. Cell Biochem Biophys 62, 273–279 (2012). https://doi.org/10.1007/s12013-011-9291-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-011-9291-4

Keywords

Search

Navigation