Molecular Biology Reports

, Volume 36, Issue 8, pp 2245–2248

Association study of a single nucleotide polymorphism in the exon 2 region of toll-like receptor 9 (TLR9) gene with susceptibility to systemic lupus erythematosus among Chinese

  • Chang-Juan Xu
  • Wen-Hui Zhang
  • Hai-Feng Pan
  • Xiang-Pei Li
  • Jian-Hua Xu
  • Dong-Qing Ye
Article

Abstract

Toll-like receptor 9 (TLR9) plays an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLR9 have been reported to be associated with a range of immune-related diseases, such as asthma, systemic lupus erythematosus (SLE) and so on. Family-based association analysis was performed to further investigate whether a single nucleotide polymorphism (rs352140) in the exon 2 region of TLR9 gene is associated with susceptibility to SLE in a Chinese population. A total of 77 patients with SLE from 74 nuclear families, aged from 12 to 63 years, were enrolled according to 1997 criteria of American College of Rheumatology (ACR), 211 family members of these patients were also included. Genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Among 77 patients with SLE, the CC, CT and TT genetype frequencies of the SNP (rs352140) were 20.8, 61.0 and 18.2%, respectively. Single loci analysis suggested that the T allele at position of rs352140 was significantly associated with the susceptibility to SLE (Z = 2.357, P = 0.018402) in dominant model, but not in additive or recessive model. Genetype analysis showed that individuals with CT genetype had greater susceptibility to SLE than those without (Z = 2.004, P = 0.045067). Our study suggests that a single nucleotide polymorphism (rs352140) in the exon 2 region of TLR9 gene may be a susceptibility factor for SLE in Chinese population.

Keywords

Systemic lupus erythematosus Polymorphism Single nucleotide TLR9 exon 2 

References

  1. 1.
    Lafyatis R, Marshak-Rothstein A (2007) Toll-like receptors and innate immune responses in systemic lupus erythematosus. Arthritis Res Ther 9:222. doi:10.1186/ar2321 CrossRefPubMedGoogle Scholar
  2. 2.
    Du X, Poltorak A, Wei Y et al (2000) Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 11:362–371PubMedGoogle Scholar
  3. 3.
    Lazarus R, Vercelli D, Palmer LJ et al (2002) Single nucleotide polymorphisms in innate immunity genes: abundant variation and potential role in complex human disease. Immunol Rev 190:9–25. doi:10.1034/j.1600-065X.2002.19002.x CrossRefPubMedGoogle Scholar
  4. 4.
    Lazarus R, Klimecki WT, Raby BA et al (2003) Single-nucleotide polymorphisms in the toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three US ethnic groups and exploratory case-control disease association studies. Genomics 81:85–91. doi:10.1016/S0888-7543(02)00022-8 CrossRefPubMedGoogle Scholar
  5. 5.
    Kelly JA, Moser KL, Harley JB (2002) The genetics of systemic lupus erythematosus: putting the pieces together. Genes Immun 3(suppl 1):S71–S85. doi:10.1038/sj.gene.6363885 CrossRefPubMedGoogle Scholar
  6. 6.
    Hur JW, Shin HD, Park BL et al (2005) Association study of toll-like receptor 9 gene polymorphism in Korean patients with systemic lupus erythematosus. Tissue Antigens 65:266–270. doi:10.1111/j.1399-0039.2005.00374.x CrossRefPubMedGoogle Scholar
  7. 7.
    Tao K, Fujii M, Tsukumo S et al (2007) Genetic variations of toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population. Ann Rheum Dis 66:905–909. doi:10.1136/ard.2006.065961 CrossRefPubMedGoogle Scholar
  8. 8.
    Ng MW, Lau CS, Chan TM et al (2005) Polymorphisms of the toll-like receptor 9 (TLR9) gene with systemic lupus erythematosus in Chinese. Rheumatology (Oxford) 44:1456–1457. doi:10.1093/rheumatology/kei120 CrossRefGoogle Scholar
  9. 9.
    Lu ZY, Jin LW, Niu ZM et al (2007) Preliminary study on polymorphism of toll-like receptor 9 gene in patients with systemic lupus erythematosus. J Shanghai jiaotong university (Medical Science) 27:1448–1450Google Scholar
  10. 10.
    Rabinowitz D, Laird N (2000) A unified apporoach to adjusting association tests for population admixture with arbitrary pedigree structure and aribitary missing marker information. Hum Hered 50:211–223. doi:10.1159/000022918 CrossRefPubMedGoogle Scholar
  11. 11.
    Anders HJ (2005) A toll for lupus. Lupus 14:417–422. doi:10.1191/0961203305lu2102rr CrossRefPubMedGoogle Scholar
  12. 12.
    Lenert PS (2006) Targeting toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus. Arthritis Res Ther 8:203. doi:10.1186/ar1888 CrossRefPubMedGoogle Scholar
  13. 13.
    Nakano S, Morimoto S, Suzuki J et al (2008) Role of pathogenic auto-antibody production by toll-like receptor 9 of B cells in active systemic lupus erythematosus. Rheumatology (Oxford) 47:145–149. doi:10.1093/rheumatology/kem327 CrossRefGoogle Scholar
  14. 14.
    Kwok SK, Lee JY, Park SH et al (2008) Dysfunctional interferon-alpha production by peripheral plasmacytoid dendritic cells upon toll-like receptor-9 stimulation in patients with systemic lupus erythematosus. Arthritis Res Ther 10:R29. doi:10.1186/ar2382 CrossRefPubMedGoogle Scholar
  15. 15.
    De Jager PL, Richardson A, Vyse TJ et al (2006) Genetic variation in toll-like receptor 9 and susceptibility to systemic lupus erythematosus. Arthritis Rheum 54:1279–1282. doi:10.1002/art.21755 CrossRefPubMedGoogle Scholar
  16. 16.
    Demirci FY, Manzi S, Ramsey-Goldman R et al (2007) Association study of toll-like receptor 5 (TLR5) and toll-like receptor 9 (TLR9) polymorphisms in systemic lupus erythematosus. J Rheumatol 34:1708–1711PubMedGoogle Scholar
  17. 17.
    Novak N, Yu CF, Bussmann C et al (2007) Putative association of a TLR9 promoter polymorphism with atopic eczema. Allergy 62:766–772PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Chang-Juan Xu
    • 1
  • Wen-Hui Zhang
    • 1
  • Hai-Feng Pan
    • 1
  • Xiang-Pei Li
    • 2
  • Jian-Hua Xu
    • 3
  • Dong-Qing Ye
    • 1
  1. 1.Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiPeople’s Republic of China
  2. 2.Department of RheumatologyAnhui Provincial HospitalHefeiPeople’s Republic of China
  3. 3.Department of Rheumatology, First Affiliated HospitalAnhui Medical UniversityHefeiChina

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