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.
Similar content being viewed by others
References
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
Du X, Poltorak A, Wei Y et al (2000) Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 11:362–371
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
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
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
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
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
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
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) 27:1448–1450
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
Anders HJ (2005) A toll for lupus. Lupus 14:417–422. doi:10.1191/0961203305lu2102rr
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
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
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
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
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 34:1708–1711
Novak N, Yu CF, Bussmann C et al (2007) Putative association of a TLR9 promoter polymorphism with atopic eczema. Allergy 62:766–772
Acknowledgments
This study was supported by grants from the National Natural Science Foundation of China (30571608, 30771848) and the key program of National Natural Science Foundation of China (30830089). We thank all families with SLE for their enthusiastic participation in this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Xu, CJ., Zhang, WH., Pan, HF. et al. 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. Mol Biol Rep 36, 2245–2248 (2009). https://doi.org/10.1007/s11033-008-9440-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-008-9440-z