Rheumatology International

, Volume 32, Issue 5, pp 1251–1255 | Cite as

A single-nucleotide polymorphism of the STAT4 gene is associated with systemic lupus erythematosus (SLE) in female Chinese population

  • Haixia Luan
  • Ping Li
  • Chunwei Cao
  • Chaohua Li
  • Chaojun Hu
  • Shulan Zhang
  • Xiaofeng Zeng
  • Fengchun Zhang
  • Changqing Zeng
  • Yongzhe Li
Original Article

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Genetic association of signal transducer and activator of transcription 4 (STAT4) with SLE susceptibility has been convincingly established in multiple populations including Asians, whereas studies of genetic relations between STAT4 polymorphisms and subphenotypes of SLE were rarely conducted. In this study, we selected Chinese female population and investigated genetic association between a polymorphism of STAT4 gene (rs7582694) and SLE. Furthermore, genetic association tests based on different subsets classified by 11 clinical manifestations were also performed. A total of 675 SLE female patients and 678 healthy controls were enrolled into this study, and SNP genotyping was performed using Sequenom’s MassArray system (Sequenom iPLEX assay). Our study showed strong evidence for genetic predisposition of rs7582694 to SLE (X2 = 23.7, OR = 0.68, 95% CI: 0.58–0.79, P = 1.13 × 10−6), while no association was observed between rs7582694 and any clinical presentations. The results of our study demonstrated that STAT4 rs7582694 SNP was significantly associated with SLE, and these results were in accordance with previous studies.

Keywords

STAT4 SLE Polymorphism Genetic susceptibility Female patients 

References

  1. 1.
    Jonsen A, Bengtsson AA, Nived O, Truedsson L, Sturfelt G (2007) Gene-environment interactions in the aetiology of systemic lupus erythematosus. Autoimmunity 40:613–617PubMedCrossRefGoogle Scholar
  2. 2.
    Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939PubMedCrossRefGoogle Scholar
  3. 3.
    Xiang YJ, Dai SM (2009) Prevalence of rheumatic diseases and disability in china. Rheumatol Int 29:481–490PubMedCrossRefGoogle Scholar
  4. 4.
    Kim I, Kim YJ, Kim K et al (2009) Genetic studies of systemic lupus erythematosus in asia: where are we now? Genes Immun 10:421–432PubMedCrossRefGoogle Scholar
  5. 5.
    Harley IT, Kaufman KM, Langefeld CD, Harley JB, Kelly JA (2009) Genetic susceptibility to SLE: New insights from fine mapping and genome-wide association studies. Nat Rev Genet 10:285–290PubMedCrossRefGoogle Scholar
  6. 6.
    Namjou B, Sestak AL, Armstrong DL et al (2009) High-density genotyping of stat4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups. Arthritis Rheum 60:1085–1095PubMedCrossRefGoogle Scholar
  7. 7.
    Korman BD, Kastner DL, Gregersen PK, Remmers EF (2008) STAT4: Genetics, mechanisms, and implications for autoimmunity. Curr Allergy Asthma Rep 8:398–403PubMedCrossRefGoogle Scholar
  8. 8.
    Bengtsson AA, Sturfelt G, Truedsson L et al (2000) Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus 9:664–671PubMedCrossRefGoogle Scholar
  9. 9.
    Lee YH, Woo JH, Choi SJ, Ji JD, Song GG (2009) Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis: a meta-analysis. Rheumatol Int 30:661–666PubMedCrossRefGoogle Scholar
  10. 10.
    Glas J, Seiderer J, Nagy M et al (2010) Evidence for STAT4 as a common autoimmune gene: Rs7574865 is associated with colonic crohn’s disease and early disease onset. PLoS One 5:e10373PubMedCrossRefGoogle Scholar
  11. 11.
    Pykalainen M, Kinos R, Valkonen S et al (2005) Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes. J Allergy Clin Immunol 115:80–87PubMedCrossRefGoogle Scholar
  12. 12.
    Rueda B, Broen J, Simeon C et al (2009) The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum Mol Genet 18:2071–2077PubMedCrossRefGoogle Scholar
  13. 13.
    Korman BD, Alba MI, Le JM et al (2008) Variant form of STAT4 is associated with primary sjogren’s syndrome. Genes Immun 9:267–270PubMedCrossRefGoogle Scholar
  14. 14.
    Hom G, Graham RR, Modrek B et al (2008) Association of systemic lupus erythematosus with c8orf13-BLK and ITGAM-ITGAX. N Engl J Med 358:900–909PubMedCrossRefGoogle Scholar
  15. 15.
    Harley JB, Alarcon-Riquelme ME, Criswell LA et al (2008) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 40:204–210PubMedCrossRefGoogle Scholar
  16. 16.
    Han JW, Zheng HF, Cui Y et al (2009) Genome-wide association study in a chinese han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 41:1234–1237PubMedCrossRefGoogle Scholar
  17. 17.
    Yang W, Shen N, Ye DQ et al (2010) Genome-wide association study in asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genet 6:e1000841PubMedCrossRefGoogle Scholar
  18. 18.
    Taylor KE, Remmers EF, Lee AT et al (2008) Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus. PLoS Genet 4:e1000084PubMedCrossRefGoogle Scholar
  19. 19.
    Sigurdsson S, Nordmark G, Garnier S et al (2008) A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5. Hum Mol Genet 17:2868–2876PubMedCrossRefGoogle Scholar
  20. 20.
    Hellquist A, Sandling JK, Zucchelli M et al (2009) Variation in STAT4 is associated with systemic lupus erythematosus in a finnish family cohort. Ann Rheum Dis 69:883–886PubMedCrossRefGoogle Scholar
  21. 21.
    Purcell S, Neale B, Todd-Brown K et al (2007) Plink: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575PubMedCrossRefGoogle Scholar
  22. 22.
    Jacob CO, Zang S, Li L et al (2003) Pivotal role of STAT4 and STAT6 in the pathogenesis of the lupus-like disease in the new zealand mixed 2328 mice. J Immunol 171:1564–1571PubMedGoogle Scholar
  23. 23.
    Vieira AR, Avila JR, Daack-Hirsch S et al (2005) Medical sequencing of candidate genes for nonsyndromic cleft lip and palate. PLoS Genet 1:e64PubMedCrossRefGoogle Scholar
  24. 24.
    Burfoot RK, Jensen CJ, Field J et al (2008) Snp mapping and candidate gene sequencing in the class I region of the HLA complex: searching for multiple sclerosis susceptibility genes in tasmanians. Tissue Antigens 71:42–50PubMedGoogle Scholar
  25. 25.
    Edghill EL, Minton JA, Groves CJ et al (2010) Sequencing of candidate genes selected by beta cell experts in monogenic diabetes of unknown aetiology. JOP 11:14–17PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Haixia Luan
    • 1
  • Ping Li
    • 1
  • Chunwei Cao
    • 2
  • Chaohua Li
    • 2
  • Chaojun Hu
    • 1
  • Shulan Zhang
    • 1
  • Xiaofeng Zeng
    • 1
  • Fengchun Zhang
    • 1
  • Changqing Zeng
    • 2
  • Yongzhe Li
    • 1
  1. 1.Department of Rheumatology and Clinical ImmunologyPeking Union Medical College Hospital, Peking Union Medical College, and Chinese Academy of Medical SciencesBeijingChina
  2. 2.Laboratory of Cancer GenomicsBeijing Institute of Genomics, Chinese Academy of SciencesBeijingChina

Personalised recommendations