Top

Published in:

Open Access 01-12-2014 | Research article

Single nucleotide polymorphisms in TNFAIP3 were associated with the risks of rheumatoid arthritis in northern Chinese Han population

Authors: Xingang Zhang, Wei Li, Xinpeng Zhang, Liang Zhao, Xiaoli Zhang, Li Jiang, Yun Guo, Jin Zhang, Zaifu Liang, Xiaofei Wang

Published in: BMC Medical Genetics | Issue 1/2014

Abstract

Background

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. It is well known that genetic and environmental risk factors and their interaction contribute to RA pathogenesis. This study aimed to investigate the association between the critical polymorphisms in the tumor necrosis factor α (TNFα)-induced protein 3(TNFAIP3) gene and the risk of RA in a large northern Chinese Han population.

Methods

A case–control study of 1280 RA patients and 1280 matched healthy controls was conducted.

Results

This study showed that carriers of the rs2230926 TG genotype or rs10499194 CT genotype had an increased risk for RA compared with those carrying the wild genotype (rs2230926: OR = 1.48, 95% CI = 1.17-1.86, p = 0.001; rs10499194: OR = 2.00, 95% CI = 1.46-2.74, p < 0.001). The combined rs2230926TG/GG or rs10499194 CT/TT were associated with an increased risk of RA (ORs were 1.50 and 2.01, 95% CIs were 1.19-1.88 and 1.47-2.74, respectively, both p < 0.001). There was not significant association between rs13207033 polymorphism and RA risk. Subset analysis stratified to gender showed that the increased risks were significant among the genotypes TG, TG/GG of rs2230926 and CT, CT/TT of rs10499194 and the corresponding ORs were 1.42 (95% CI = 1.10-1.83, p = 0.006), 1.44(95% CI = 1.12-1.85, p = 0.004), 1.52(95% CI = 1.05-2.20, p = 0.026) and 1.52(95% CI = 1.06-2.19, p = 0.023) in the female population. Stratified analyses by age found that rs2230926(TG, TG/GG) and rs10499194(CT, CT/TT) polymorphisms were associated with RA risks in population ≤53 years old and among >53 years old only rs10499194(CT, TT, CT/TT) polymorphism had significant results. The interaction analysis suggested that individuals with both risk genotypes of the two SNPs have a higher elevated risk of RA than those with only one of them (ORs were 3.44 compared to 1.74 and 1.35). The haplotype results showed that individuals with the rs2230926G-rs13207033G-rs10499194C haplotype were associated with increased risks of RA (OR = 1.37, 95% CI = 1.08-1.74, p = 0.010).

Conclusions

Rs10499194 and rs2230926 polymorphisms in the TNFAIP3 gene region may be susceptibility factors for rheumatoid arthritis in the northern Chinese Han population.

Mahdi H, Fisher BA, Källberg H, Plant D, Malmström V, Rönnelid J, Charles P, Ding B, Alfredsson L, Padyukov L, Symmons DP, Venables PJ, Klareskog L, Lundberg K: Specific interaction between genotype, smoking and autoimmunity to citrullinatedenolase in the etiology of rheumatoid arthritis. Nat Genet. 2009, 41 (12): 1319-1324. 10.1038/ng.480.CrossRefPubMed

MacGregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Aho K, Silman AJ: Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 2000, 43 (1): 30-37. 10.1002/1529-0131(200001)43:1<30::AID-ANR5>3.0.CO;2-B.CrossRefPubMed

Coornaert B, Carpentier I, Beyaert R: A20: central gatekeeper in inflammation and immunity. J Biol Chem. 2009, 284 (13): 8217-8221. 10.1074/jbc.R800032200.CrossRefPubMedPubMedCentral

Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM: De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004, 430 (7000): 694-699. 10.1038/nature02794.CrossRefPubMed

Vereecke L, Beyaert R, van Loo G: The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol. 2009, 30 (8): 383-391. 10.1016/j.it.2009.05.007.CrossRefPubMed

Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A: Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice. Science. 2000, 289 (5488): 2350-2354. 10.1126/science.289.5488.2350.CrossRefPubMedPubMedCentral

Matmati M, Jacques P, Maelfait J, Verheugen E, Kool M, Sze M, Geboes L, Louagie E, Mc Guire C, Vereecke L, Chu Y, Boon L, Staelens S, Matthys P, Lambrecht BN, Schmidt-Supprian M, Pasparakis M, Elewaut D, Beyaert R, van Loo G: A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat Genet. 2011, 43 (9): 908-912. 10.1038/ng.874.CrossRefPubMed

Chu Y, Vahl JC, Kumar D, Heger K, Bertossi A, Wójtowicz E, Soberon V, Schenten D, Mack B, Reutelshöfer M, Beyaert R, Amann K, van Loo G, Schmidt-Supprian M: B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice. Blood. 2011, 117 (7): 2227-2236. 10.1182/blood-2010-09-306019.CrossRefPubMed

Kool M, van Loo G, Waelput W, De Prijck S, Muskens F, Sze M, van Praet J, Branco-Madeira F, Janssens S, Reizis B, Elewaut D, Beyaert R, Hammad H, Lambrecht BN: The ubiquitin-editing protein A20 prevents dendritic cell activation, recognition of apoptotic cells, and systemic autoimmunity. Immunity. 2011, 35 (1): 82-96. 10.1016/j.immuni.2011.05.013.CrossRefPubMed

10.

Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, Barrera J, Huang EJ, Hou B, Malynn BA, Reizis B, DeFranco A, Criswell LA, Nakamura MC, Ma A: Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol. 2011, 12 (12): 1184-1193. 10.1038/ni.2135.CrossRefPubMedPubMedCentral

11.

Thomson W, Barton A, Ke X, Eyre S, Hinks A, Bowes J, Donn R, Symmons D, Hider S, Bruce IN, Wilson AG, Marinou I, Morgan A, Emery P, Consortium YEAR, Carter A, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Strachan D, Worthington J, Wellcome Trust Case Control Consortium: Rheumatoid arthritis association at 6q23. Nat Genet. 2007, 39 (12): 1431-1433. 10.1038/ng.2007.32.CrossRefPubMedPubMedCentral

12.

Plenge RM, Cotsapas C, Davies L, Price AL, de Bakker PI, Maller J, Pe'er I, Burtt NP, Blumenstiel B, DeFelice M, Parkin M, Barry R, Winslow W, Healy C, Graham RR, Neale BM, Izmailova E, Roubenoff R, Parker AN, Glass R, Karlson EW, Maher N, Hafler DA, Lee DM, Seldin MF, Remmers EF, Lee AT, Padyukov L, Alfredsson L, Coblyn J, et al: Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet. 2007, 39 (12): 1477-1482. 10.1038/ng.2007.27.CrossRefPubMedPubMedCentral

13.

Dieguez-Gonzalez R, Calaza M, Perez-Pampin E, Balsa A, Blanco FJ, Cañete JD, Caliz R, Carreño L, de la Serna AR, Fernandez-Gutierrez B, Ortiz AM, Herrero-Beaumont G, Pablos JL, Narvaez J, Navarro F, Marenco JL, Gomez-Reino JJ, Gonzalez A: Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-κB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility. Arthritis Res Ther. 2009, 11 (2): R42-10.1186/ar2650.CrossRefPubMedPubMedCentral

14.

Lodolce JP, Kolodziej LE, Rhee L, Kariuki SN, Franek BS, McGreal NM, Logsdon MF, Bartulis SJ, Perera MA, Ellis NA, Adams EJ, Hanauer SB, Jolly M, Niewold TB, Boone DL: African-derived genetic polymorph-isms in TNFAIP3 mediate risk for autoimmunity. J Immunol. 2010, 184 (12): 7001-7009. 10.4049/jimmunol.1000324.CrossRefPubMedPubMedCentral

15.

Hughes LB, Reynolds RJ, Brown EE, Kelley JM, Thomson B, Conn DL, Jonas BL, Westfall AO, Padilla MA, Callahan LF, Smith EA, Brasington RD, Edberg JC, Kimberly RP, Moreland LW, Plenge RM, Bridges SL: Most common single-nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans. Arthritis Rheum. 2010, 62 (12): 3547-3553. 10.1002/art.27732.CrossRefPubMedPubMedCentral

16.

Ben Hamad M, Cornelis F, Maalej A, Petit-Teixeira E: Tunisian case–control association study of a 6q polymorphism in rheumatoid arthritis. Rheumatol Int. 2012, 32 (6): 1849-1850. 10.1007/s00296-011-1996-6.CrossRefPubMed

17.

Han TU, Bang SY, Kang C, Bae SC: TRAF1 polymorphisms associated with rheumatoid arthritis susceptibility in Asians and in Caucasians. Arthritis Rheum. 2009, 60 (9): 2577-2584. 10.1002/art.24759.CrossRefPubMed

18.

Shimane K, Kochi Y, Horita T, Ikari K, Amano H, Hirakata M, Okamoto A, Yamada R, Myouzen K, Suzuki A, Kubo M, Atsumi T, Koike T, Takasaki Y, Momohara S, Yamanaka H, Nakamura Y, Yamamoto K: The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population. Arthritis Rheum. 2010, 62 (2): 574-579.PubMed

19.

Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS: The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31 (3): 315-324. 10.1002/art.1780310302.CrossRefPubMed

20.

Shi YY, He L: SHEs is, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005, 15 (2): 97-98. 10.1038/sj.cr.7290272.CrossRefPubMed

21.

Li Z, Zhang Z, He Z, Tang W, Li T, Zeng Z, He L, Shi Y: A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http://analysis.bio-x.cn). Cell Res. 2009, 19 (4): 519-523. 10.1038/cr.2009.33.CrossRefPubMed

22.

Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K: Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003, 34 (4): 395-402. 10.1038/ng1206.CrossRefPubMed

23.

Suzuki A, Yamada R, Kochi Y, Sawada T, Okada Y, Matsuda K, Kamatani Y, Mori M, Shimane K, Hirabayashi Y, Takahashi A, Tsunoda T, Miyatake A, Kubo M, Kamatani N, Nakamura Y, Yamamoto K: Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population. Nat Genet. 2008, 40 (10): 1224-1229. 10.1038/ng.205.CrossRefPubMed

24.

Lee HS, Korman BD, Le JM, Kastner DL, Remmers EF, Gregersen PK, Bae SC: Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations. Arthritis Rheum. 2009, 60 (2): 364-371. 10.1002/art.24245.CrossRefPubMedPubMedCentral

25.

Wellcome Trust Case Control Consortium: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007, 447 (7145): 661-678. 10.1038/nature05911.CrossRef

26.

Orozco G, Hinks A, Eyre S, Ke X, Gibbons LJ, Bowes J, Flynn E, Martin P, Wilson AG, Bax DE, Morgan AW, Emery P, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Thomson W, Barton A, Worthington J, Wellcome Trust Case Control Consortium: Combined effects of three independent SNPs greatly increase the risk estimate for RA at6q23. Hum Mol Genet. 2009, 18 (14): 2693-2699. 10.1093/hmg/ddp193.CrossRefPubMedPubMedCentral

27.

Bowes J, Lawrence R, Eyre S, Panoutsopoulou K, Orozco G, Elliott KS, Ke X, Morris AP, Thomson W, Worthington J, Barton A, Zeggini E, UKRAG: Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritis. Hum Genet. 2010, 128 (6): 627-633. 10.1007/s00439-010-0889-1.CrossRefPubMedPubMedCentral

28.

Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W, Shifrin N, Petri MA, Kamboh MI, Manzi S, Seldin MF, Gregersen PK, Behrens TW, Ma A, Kwok PY, Criswell LA: Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet. 2008, 40 (9): 1062-1064. 10.1038/ng.202.CrossRefPubMedPubMedCentral

29.

Perdigones N, Lamas JR, Vigo AG, de la Concha EG, Jover JA, Urcelay E, Gutiérrez BF, Martínez A: 6q23 polymorphisms in rheumatoid arthritis Spanish patients. Rheumatology (Oxford). 2009, 48 (6): 618-621. 10.1093/rheumatology/kep053.CrossRef

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/15/56/prepub

Title: Single nucleotide polymorphisms in TNFAIP3 were associated with the risks of rheumatoid arthritis in northern Chinese Han population
Authors: Xingang Zhang
Wei Li
Xinpeng Zhang
Liang Zhao
Xiaoli Zhang
Li Jiang
Yun Guo
Jin Zhang
Zaifu Liang
Xiaofei Wang
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2014
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-15-56

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Single nucleotide polymorphisms in TNFAIP3 were associated with the risks of rheumatoid arthritis in northern Chinese Han population

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

EDAR-induced hypohidrotic ectodermal dysplasia: a clinical study on signs and symptoms in individuals with a heterozygous c.1072C > T mutation

The impact of coronary artery disease risk loci on ischemic heart failure severity and prognosis: association analysis in the COntrolled ROsuvastatin multiNAtional trial in heart failure (CORONA)

De novo deletion of chromosome 11q12.3 in monozygotic twins affected by Poland Syndrome

Alternative splicing in osteoclasts and Paget’s disease of bone

Allelic expression analysis of the osteoarthritis susceptibility locus that maps to chromosome 3p21 reveals cis-acting eQTLs at GNL3 and SPCS1

Analysis of single-nucleotide polymorphisms (SNPs) in human CYP3A4 and CYP3A5 genes: potential implications for the metabolism of HIV drugs