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01-08-2009 | Original Article

Association between the rs2004640 functional polymorphism of interferon regulatory factor 5 and systemic lupus erythematosus: a meta-analysis

Authors: Young Ho Lee, Gwan Gyu Song

Published in: Rheumatology International | Issue 10/2009

Abstract

The aim of this study is to determine whether the functional interferon regulatory factor 5 (IRF5) polymorphism, rs2004640, confers susceptibility to systemic lupus erythematosus (SLE) in multiple ethic populations. A meta-analysis was conducted on the T allele of the IRF5 rs2004640 polymorphism and 12 studies were included in the meta-analysis. Meta-analysis revealed an association between SLE and the IRF5 rs2004640 T allele in all subjects without inter-study heterogeneity (OR 1.429, 95% CI 1.359–1.503, P < 0.001). The IRF5 rs2004640 T allele was significantly associated with SLE in European and Asians. The Asian population had a much lower prevalence of the T allele (34.4%) than any other population studied. and Europeans had the highest frequency of the IRF5 rs2004640 T allele (51.8%). In conclusion, this meta-analysis confirms that the IRF5 rs2004640 polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.

Harley JB, Kelly JA, Kaufman KM (2006) Unraveling the genetics of systemic lupus erythematosus. Springer Semin Immunopathol 28:119–130. doi:10.1007/s00281-006-0040-5 PubMedCrossRef

Banchereau J, Pascual V (2006) Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25:383–392. doi:10.1016/j.immuni.2006.08.010 PubMedCrossRef

Taniguchi T, Ogasawara K, Takaoka A, Tanaka N (2001) IRF family of transcription factors as regulators of host defense. Annu Rev Immunol 19:623–655. doi:10.1146/annurev.immunol.19.1.623 PubMedCrossRef

Kawasaki A, Kyogoku C, Ohashi J, Miyashita R, Hikami K, Kusaoi M, Tokunaga K, Takasaki Y, Hashimoto H, Behrens TW, Tsuchiya N (2008) Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population: support for a crucial role of intron 1 polymorphisms. Arthritis Rheum 58:826–834. doi:10.1002/art.23216 PubMedCrossRef

Sigurdsson S, Goring HH, Kristjansdottir G, Milani L, Nordmark G, Sandling JK, Eloranta ML, Feng D, Sangster-Guity N, Gunnarsson I, Svenungsson E, Sturfelt G, Jonsen A, Truedsson L, Barnes BJ, Alm G, Ronnblom L, Syvanen AC (2008) Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus erythematosus. Hum Mol Genet 17:872–881. doi:10.1093/hmg/ddm359 PubMedCrossRef

Reddy MV, Velazquez-Cruz R, Baca V, Lima G, Granados J, Orozco L, Alarcon-Riquelme ME (2007) Genetic association of IRF5 with SLE in Mexicans: higher frequency of the risk haplotype and its homozygozity than Europeans. Hum Genet 121:721–727. doi:10.1007/s00439-007-0367-6 PubMedCrossRef

Demirci FY, Manzi S, Ramsey-Goldman R, Minster RL, Kenney M, Shaw PS, Dunlop-Thomas CM, Kao AH, Rhew E, Bontempo F, Kammerer C, Kamboh MI (2007) Association of a common interferon regulatory factor 5 (IRF5) variant with increased risk of systemic lupus erythematosus (SLE). Ann Hum Genet 71:308–311. doi:10.1111/j.1469-1809.2006.00336.x PubMedCrossRef

Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, Gonzalez Escribano MF, Pons-Estel B, Petri M, Daly M, Gregersen PK, Martin J, Altshuler D, Behrens TW, Alarcon-Riquelme ME (2006) A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 38:550–555. doi:10.1038/ng1782 PubMedCrossRef

Sigurdsson S, Nordmark G, Goring HH, Lindroos K, Wiman AC, Sturfelt G, Jonsen A, Rantapaa-Dahlqvist S, Moller B, Kere J, Koskenmies S, Widen E, Eloranta ML, Julkunen H, Kristjansdottir H, Steinsson K, Alm G, Ronnblom L, Syvanen AC (2005) Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Genet 76:528–537. doi:10.1086/428480 PubMedCrossRef

10.

Shin HD, Sung YK, Choi CB, Lee SO, Lee HW, Bae SC (2007) Replication of the genetic effects of IFN regulatory factor 5 (IRF5) on systemic lupus erythematosus in a Korean population. Arthritis Res Ther 9:R32. doi:10.1186/ar2152 PubMedCrossRef

11.

Kelly JA, Kelley JM, Kaufman KM, Kilpatrick J, Bruner GR, Merrill JT, James JA, Frank SG, Reams E, Brown EE, Gibson AW, Marion MC, Langefeld CD, Li QZ, Karp DR, Wakeland EK, Petri M, Ramsey-Goldman R, Reveille JD, Vila LM, Alarcon GS, Kimberly RP, Harley JB, Edberg JC (2008) Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans. Genes Immun 9:187–194. doi:10.1038/gene.2008.4 PubMedCrossRef

12.

Siu HO, Yang W, Lau CS, Chan TM, Wong RW, Wong WH, Lau YL, Alarcon-Riquelme ME (2008) Association of a haplotype of IRF5 gene with systemic lupus erythematosus in Chinese. J Rheumatol 35:360–362PubMed

13.

Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMed

14.

Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. doi:10.1002/sim.1186 PubMedCrossRef

15.

Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315:1533–1537PubMed

16.

Harley JB, Alarcon-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL, Tsao BP, Vyse TJ, Langefeld CD, Nath SK, Guthridge JM, Cobb BL, Mirel DB, Marion MC, Williams AH, Divers J, Wang W, Frank SG, Namjou B, Gabriel SB, Lee AT, Gregersen PK, Behrens TW, Taylor KE, Fernando M, Zidovetzki R, Gaffney PM, Edberg JC, Rioux JD, Ojwang JO, James JA, Merrill JT, Gilkeson GS, Seldin MF, Yin H, Baechler EC, Li QZ, Wakeland EK, Bruner GR, Kaufman KM, Kelly JA (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. doi:10.1038/ng.81 PubMedCrossRef

17.

Ferreiro-Neira I, Calaza M, Alonso-Perez E, Marchini M, Scorza R, Sebastiani GD, Blanco FJ, Rego I, Pullmann R Jr, Pullmann R, Kallenberg CG, Bijl M, Skopouli FN, Mavromati M, Migliaresi S, Barizzone N, Ruzickova S, Dostal C, Schmidt RE, Witte T, Papasteriades C, Kappou-Rigatou I, Endreffy E, Kovacs A, Ordi-Ros J, Balada E, Carreira P, Gomez-Reino JJ, Gonzalez A (2007) Opposed independent effects and epistasis in the complex association of IRF5 to SLE. Genes Immun 8:429–438. doi:10.1038/sj.gene.6364407 PubMedCrossRef

18.

Kozyrev SV, Lewen S, Reddy PM, Pons-Estel B, Witte T, Junker P, Laustrup H, Gutierrez C, Suarez A, Francisca Gonzalez-Escribano M, Martin J, Alarcon-Riquelme ME (2007) Structural insertion/deletion variation in IRF5 is associated with a risk haplotype and defines the precise IRF5 isoforms expressed in systemic lupus erythematosus. Arthritis Rheum 56:1234–1241. doi:10.1002/art.22497 PubMedCrossRef

19.

Graham RR, Kyogoku C, Sigurdsson S, Vlasova IA, Davies LR, Baechler EC, Plenge RM, Koeuth T, Ortmann WA, Hom G, Bauer JW, Gillett C, Burtt N, Cunninghame Graham DS, Onofrio R, Petri M, Gunnarsson I, Svenungsson E, Ronnblom L, Nordmark G, Gregersen PK, Moser K, Gaffney PM, Criswell LA, Vyse TJ, Syvanen AC, Bohjanen PR, Daly MJ, Behrens TW, Altshuler D (2007) Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci USA 104:6758–6763. doi:10.1073/pnas.0701266104 PubMedCrossRef

20.

Jacob CO, Reiff A, Armstrong DL, Myones BL, Silverman E, Klein-Gitelman M, McCurdy D, Wagner-Weiner L, Nocton JJ, Solomon A, Zidovetzki R (2007) Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform. Arthritis Rheum 56:4164–4173. doi:10.1002/art.23060 PubMedCrossRef

21.

Cunninghame Graham DS, Manku H, Wagner S, Reid J, Timms K, Gutin A, Lanchbury JS, Vyse TJ (2007) Association of IRF5 in UK SLE families identifies a variant involved in polyadenylation. Hum Mol Genet 16:579–591. doi:10.1093/hmg/ddl469 PubMedCrossRef

22.

Lee YH, Nath SK (2005) Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet 118:434–443. doi:10.1007/s00439-005-0073-1 PubMedCrossRef

23.

Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S, Lee AT, Chung SA, Ferreira RC, Pant PV, Ballinger DG, Kosoy R, Demirci FY, Kamboh MI, Kao AH, Tian C, Gunnarsson I, Bengtsson AA, Rantapaa-Dahlqvist S, Petri M, Manzi S, Seldin MF, Ronnblom L, Syvanen AC, Criswell LA, Gregersen PK, Behrens TW (2008) Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 358:900–909. doi:10.1056/NEJMoa0707865 PubMedCrossRef

24.

Honda K, Yanai H, Takaoka A, Taniguchi T (2005) Regulation of the type I IFN induction: a current view. Int Immunol 17:1367–1378. doi:10.1093/intimm/dxh318 PubMedCrossRef

25.

Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, Kano S, Honda K, Ohba Y, Mak TW, Taniguchi T (2005) Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434:243–249. doi:10.1038/nature03308 PubMedCrossRef

26.

Tackey E, Lipsky PE, Illei GG (2004) Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus 13:339–343. doi:10.1191/0961203304lu1023oa PubMedCrossRef

27.

Kozyrev SV, Alarcon-Riquelme ME (2007) The genetics and biology of Irf5-mediated signaling in lupus. Autoimmunity 40:591–601. doi:10.1080/08916930701510905 PubMedCrossRef

28.

Mancl ME, Hu G, Sangster-Guity N, Olshalsky SL, Hoops K, Fitzgerald-Bocarsly P, Pitha PM, Pinder K, Barnes BJ (2005) Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms. Multiple isoforms with distinct cell type-specific expression, localization, regulation, and function. J Biol Chem 280:21078–21090. doi:10.1074/jbc.M500543200 PubMedCrossRef

Title: Association between the rs2004640 functional polymorphism of interferon regulatory factor 5 and systemic lupus erythematosus: a meta-analysis
Authors: Young Ho Lee
Gwan Gyu Song
Publication date: 01-08-2009
Publisher: Springer-Verlag
Published in: Rheumatology International / Issue 10/2009
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-008-0801-7

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