Abstract
Systemic lupus erythematosus (SLE) is a complex systemic disease influenced by genetic and environmental factors. The exact pathogenesis of SLE is still unknown. Recently, several genome-wide association studies (GWA) in European population have found many novel susceptibility genes for SLE including TNFAIP3. In order to examine whether TNFAIP3 is associated with SLE in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system. Highly significant association between SNP rs2230926 and SLE of Chinese Han was detected [OR = 1.65, 95% confidence interval (CI): 1.392–1.986, P = 2.03 × 10−8]. Interestingly, rs2230926 of TNFAIP3 was also associated with arthritis, ANA and some other subphenotypes of the disease. Our findings suggest that SNP rs2230926 in the TNFAIP3 might be a common genetic factor for SLE within different populations in terms of Chinese Han and European population.
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References
Lau CS, Yin G, Mok MY (2006) Ethnic and geographical differences in systemic lupus erythematosus: an overview. Lupus 15:715–719
Lockshin MD (2006) Sex differences in autoimmune disease. Lupus 15:753–756
Uribe AG, McGwin G Jr, Reveille JD, Alarcón GS (2004) What have we learned from a 10-year experience with the LUMINA (Lupus in Minorities; Nature vs. nurture) cohort? Where are we heading? Autoimmun Rev 3:321–329
Cunninghame Graham DS, Graham RR, Manku H et al (2008) Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus. Nat Genet 40:83–89
Nath SK, Han S, Kim-Howard X et al (2008) A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet 40:152–154
Hom G, Graham RR, Modrek B et al (2008) Association of systemic lupus erythematosus with C8orf13–BLK and ITGAM–TGAX. N Engl J Med 358:900–909
Kozyrev SV, Abelson AK, Wojcik J et al (2008) Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat Genet 40:211–216
Graham RR, Cotsapas C, Davies L et al (2008) Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet 40:1059–1061
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 40:204–210
Plenge RM, Cotsapas C, Davies L et al (2007) Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet 39:1477–1482
Thomson W, Barton A, Ke X et al (2007) Rheumatoid arthritis association at 6q23. Nat Genet 39:1431–1433
Musone SL, Taylor KE, Lu TT et al (2008) Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet 40:1062–1064
Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725
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 81:559–575
Block SR, Winfield JB, Lockshin MD, D’Angelo WA, Christian CL (1975) Studies of twins with systemic lupus erythematosus: a review of the literature and presentation of 12 additional sets. Am J Med 59:533–552
Dieguez-Gonzalez R, Calaze M, Perez-Pampin E et al (2009) Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-kappaB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility. Arthritis Res Ther 11:R42
Dixit VM, Green S, Sarma V et al (1990) Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. J Biol Chem 265:2973–2978
Lee EG, Boone DL, Chai S et al (2000) Failure to regulate TNF-induced NF-kappa-B and cell death responses in A20-deficient mice. Science 289:2350–2354
Vendrell JA, Ghayad S, Ben-Larbi S, Dumontet C, Mechti N, Cohen PA (2007) A20/TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells. Oncogene 26:4656–4667
Song XT, Evel-Kabler K, Shen L, Rollins L, Huang XF, Chen SY (2008) A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell-mediated suppression. Nat Med 14:258–265
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:e1000084
Yang W, Nq P, Zhao M et al (2009) Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. Genes and Immun 10:219–226
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We are most grateful to all the members for their voluntary participation in this study.
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L.-Q. Cai and Z.-X. Wang contributed equally to this study.
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Cai, LQ., Wang, ZX., Lu, WS. et al. A single-nucleotide polymorphism of the TNFAIP3 gene is associated with systemic lupus erythematosus in Chinese Han population. Mol Biol Rep 37, 389–394 (2010). https://doi.org/10.1007/s11033-009-9818-6
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DOI: https://doi.org/10.1007/s11033-009-9818-6