Archives of Dermatological Research

, Volume 310, Issue 9, pp 711–728 | Cite as

Comprehensive assessment of the association between genes on JAK-STAT pathway (IFIH1, TYK2, IL-10) and systemic lupus erythematosus: a meta-analysis

  • Qiong Yin
  • Liang-Cai Wu
  • Lu Zheng
  • Ming-Yu Han
  • Li-Ya Hu
  • Pian-Pian Zhao
  • Wei-Yang Bai
  • Xiao-Wei Zhu
  • Jiang-Wei Xia
  • Xiao-Bo Wang
  • Xing-Wei Zhang
  • Hou-Feng ZhengEmail author
Original Paper


Previous studies have reported that genes relating to JAK-STAT pathway (IFIH1, TYK2 and IL-10) conferred the susceptibility to SLE. In this study, we performed a meta-analysis (including 43 studies) to evaluate the association between IFIH1 (9288 patients and 24,040 controls), TYK2 (4928 patients and 11,536 controls), IL-10 (3623 patients and 4907 controls) polymorphisms and systemic lupus erythematosus (SLE) in a comprehensive way. We found that IFIH1 rs1990760_T allele was associated with risk of SLE in overall population under three models (allelic: P = 2.56 × 10−11, OR 1.135, 95% CI 1.094–1.179, dominant: P = 1.8 × 10−8, OR 1.203, 95% CI 1.128–1.284, recessive: P = 2.6 × 10−7, OR 1.163, 95% CI 1.098–1.231). A strong association had been observed between TYK2 polymorphism rs2304256_C allele and SLE in Europeans (P = 5.82 × 10−5, OR 1.434, 95% CI 1.203–1.710). When coming to overall population, TYK2 rs2304256_C showed a significant association with SLE under recessive model (P = 8.05 × 10−3, OR 1.314, 95% CI 1.074–1.608). However, the other two SNPs (rs12720270, rs280519) of TYK2 were not significant. The results also indicated an association between IL-10 rs1800896_G allele and SLE in Asians under recessive model (P = 4.65 × 10−3, OR 2.623, 95% CI 1.346–5.115), while, IL-10 rs1800896_G had a trend of association with SLE in European population in dominant model (P = 1.21 × 10−2, OR 1.375, 95% CI 1.072–1.764). In addition, we found IL-10 rs1800896 GG homozygote might be associated with increased susceptibility to SLE (GG vs AA, P = 4.65 × 10−3, OR 1.539, 95% CI 1.142–2.072). We concluded that IFIH1 rs1990760_T and TYK2 rs2304256_C alleles were significantly associated with SLE, and IL-10 rs1800896 GG homozygote might have an enhancement effect on SLE risk.


IFIH1 TYK2 IL-10 Meta-analysis Systemic lupus erythematosus 



This study was supported by the National Natural Science Foundation of China (81501145, 81871831), the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars of China (LR17H070001), the State Key Development Program for Basic Research of China (973 Program, 2014CB541701), the “Thousand Talents” Program, the HZNUARI-Pilot Research Grant and Guangdong Provincial Science and Technology Plan project (2014A020212434). The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the peer reviewers for their thorough and helpful review of this manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no competing interests that might be perceived to influence the results and/or discussion reported in this paper. This study re-analyzed the previous published data, therefore, this study did not involve origin human participants.

Supplementary material

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Supplementary material 1 (PDF 3775 KB)


  1. 1.
    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 76:528–537CrossRefGoogle Scholar
  2. 2.
    Chung SA, Taylor KE, Graham RR, Nititham J, Lee AT, Ortmann WA, Jacob CO, Alarcon-Riquelme ME, Tsao BP, Harley JB, Gaffney PM, Moser KL, Slegen, Petri M, Demirci FY, Kamboh MI, Manzi S, Gregersen PK, Langefeld CD, Behrens TW, Criswell LA (2011) Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production. PLoS Genet 7:e1001323CrossRefGoogle Scholar
  3. 3.
    Danchenko N, Satia JA, Anthony MS (2006) Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 15:308–318CrossRefGoogle Scholar
  4. 4.
    Zhu XW, Wang Y, Wei YH, Zhao PP, Wang XB, Rong JJ, Zhong WY, Zhang XW, Wang L, Zheng HF (2016) Comprehensive assessment of the association between FCGRs polymorphisms and the risk of systemic lupus erythematosus: evidence from a meta-analysis. Sci Rep 6:31617CrossRefGoogle Scholar
  5. 5.
    Cui Y, Sheng Y, Zhang X (2013) Genetic susceptibility to SLE: recent progress from GWAS. J Autoimmun 41:25–33CrossRefGoogle Scholar
  6. 6.
    Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, Ortmann W, Kosoy R, Ferreira RC, Nordmark G (2009) A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 41:1228–1233CrossRefGoogle Scholar
  7. 7.
    International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley JB, Alarcón-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL, Tsao BP, Vyse TJ, Langefeld CD, Nath SKGJ, 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 (2008) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 40:204–210CrossRefGoogle Scholar
  8. 8.
    Kozyrev SV, Abelson AK, Wojcik J, Zaghlool A, Linga Reddy MV, Sanchez E, Gunnarsson I, Svenungsson E, Sturfelt G, Jonsen A, Truedsson L, Pons-Estel BA, Witte T, D’Alfonso S, Barizzone N, Danieli MG, Gutierrez C, Suarez A, Junker P, Laustrup H, Gonzalez-Escribano MF, Martin J, Abderrahim H, Alarcon-Riquelme ME (2008) Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat Genet 40:211–216CrossRefGoogle Scholar
  9. 9.
    Prokunina L, Castillejo-López C, Öberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdóttir H, Gröndal G, Bolstad AI, Svenungsson E, Lundberg I, Sturfelt G, Jönssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcón-Segovia D, Steinsson K, Alarcón-Riquelme ME (2002) A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet 32:666–669CrossRefGoogle Scholar
  10. 10.
    Guo BR, Rong JJ, Wei YH, Zhong WY, Li CS, Liu M, Li W, Wang XB, Wang L, Zheng HF (2015) Ethnicity-stratified analysis of the association between IL-18 polymorphisms and systemic lupus erythematosus in a European population: a meta-analysis. Arch Dermatol Res 307:747–755CrossRefGoogle Scholar
  11. 11.
    Han JW, Zheng HF, Cui Y, Sun LD, Ye DQ, Hu Z, Xu JH, Cai ZM, Huang W, Zhao GP, Xie HF, Fang H, Lu QJ, Xu JH, Li XP, Pan YF, Deng DQ, Zeng FQ, Ye ZZ, Zhang XY, Wang QW, Hao F, Ma L, Zuo XB, Zhou FS, Du WH, Cheng YL, Yang JQ, Shen SK, Li J, Sheng YJ, Zuo XX, Zhu WF, Gao F, Zhang PL, Guo Q, Li B, Gao M, Xiao FL, Quan C, Zhang C, Zhang Z, Zhu KJ, Li Y, Hu DY, Lu WS, Huang JL, Liu SX, Li H, Ren YQ, Wang ZX, Yang CJ, Wang PG, Zhou WM, Lv YM, Zhang AP, Zhang SQ, Lin D, Li Y, Low HQ, Shen M, Zhai ZF, Wang Y, Zhang FY, Yang S, Liu JJ, Zhang XJ (2009) Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 41:1234–1237CrossRefGoogle Scholar
  12. 12.
    Lee YH, Bae SC, Choi SJ, Ji JD, Song G (2012) Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis. Mol Biol Rep 39:10627–10635CrossRefGoogle Scholar
  13. 13.
    Yang W, Shen N, Ye DQ, Liu Q, Zhang Y, Qian XX, Hirankarn N, Ying D, Pan HF, Mok CC, Chan TM, Wong RW, Lee KW, Mok MY, Wong SN, Leung AM, Li XP, Avihingsanon Y, Wong CM, Lee TL, Ho MH, Lee PP, Chang YK, Li PH, Li RJ, Zhang L, Wong WH, Ng IO, Lau CS, Sham PC, Lau YL, Asian Lupus Genetics C (2010) Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genet 6:e1000841CrossRefGoogle Scholar
  14. 14.
    Azevedo Silva JD, Addobbati C, Sandrin-Garcia P, Crovella S (2014) Systemic lupus erythematosus: old and new susceptibility genes versus clinical manifestations. Curr Genom 15:52–65CrossRefGoogle Scholar
  15. 15.
    Kariuki SN, Ghodke-Puranik Y, Dorschner JM, Chrabot BS, Kelly JA, Tsao BP, Kimberly RP, Alarconriquelme ME, Jacob CO, Criswell LA (2015) Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. Genes Immun 16:15–23CrossRefGoogle Scholar
  16. 16.
    Davies RC, Pettijohn K, Fike F, Wang J, Nahas SA, Tunuguntla R, Hu H, Gatti RA, McCurdy D (2012) Defective DNA double-strand break repair in pediatric systemic lupus erythematosus. Arthritis Rheum 64:568–578CrossRefGoogle Scholar
  17. 17.
    Crow MK, Olferiev M, Kirou KA (2015) Targeting of type I interferon in systemic autoimmune diseases. Transl Res 165:296–305CrossRefGoogle Scholar
  18. 18.
    Robinson T, Kariuki SN, Franek BS, Kumabe M, Kumar AA, Badaracco M, Mikolaitis RA, Guerrero G, Utset TO, Drevlow BE, Zaacks LS, Grober JS, Cohen LM, Kirou KA, Crow MK, Jolly M, Niewold TB (2011) Autoimmune disease risk variant of IFIH1 is associated with increased sensitivity to IFN-alpha and serologic autoimmunity in lupus patients. J Immunol 187:1298–1303CrossRefGoogle Scholar
  19. 19.
    de Azevedo Silva J, Tavares NA, Santos MM, Moura R, Guimaraes RL, Araujo J, Crovella S, Brandao LA (2015) Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III. Genet Mol Res 14:17730–17738CrossRefGoogle Scholar
  20. 20.
    Sutherland A, Davies J, Owen CJ, Vaikkakara S, Walker C, Cheetham TD, James RA, Perros P, Donaldson PT, Cordell HJ, Quinton R, Pearce SH (2007) Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves’ disease susceptibility. J Clin Endocrinol Metab 92:3338–3341CrossRefGoogle Scholar
  21. 21.
    Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2, Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, Barton A, Band G, Bellenguez C, Bergboer JG, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Cork MJ, Corvin A, Deloukas P, Dilthey A, Duncanson A, Edkins S, Estivill X, Fitzgerald O, Freeman C, Giardina E, Gray E, Hofer A, Huffmeier U, Hunt SE, Irvine AD, Jankowski J, Kirby B, Langford C, Lascorz J, Leman J, Leslie S, Mallbris L, Markus HS, Mathew CG, McLean WH, McManus R, Mossner R, Moutsianas L, Naluai AT, Nestle FO, Novelli G, Onoufriadis A, Palmer CN, Perricone C, Pirinen M, Plomin R, Potter SC, Pujol RM, Rautanen A, Riveira-Munoz E, Ryan AW, Salmhofer W, Samuelsson L, Sawcer SJ, Schalkwijk J, Smith CH, Stahle M, Su Z, Tazi-Ahnini R, Traupe H, Viswanathan AC, Warren RB, Weger W, Wolk K, Wood N, Worthington J, Young HS, Zeeuwen PL, Hayday A, Burden AD, Griffiths CE, Kere J, Reis A, McVean G, Evans DM, Brown MA, Barker JN, Peltonen L, Donnelly P, Trembath RC (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 42:985–990CrossRefGoogle Scholar
  22. 22.
    Smyth DJ, Cooper JD, Bailey R, Field S, Burren O, Smink LJ, Guja C, Ionescu-Tirgoviste C, Widmer B, Dunger DB, Savage DA, Walker NM, Clayton DG, Todd JA (2006) A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet 38:617–619CrossRefGoogle Scholar
  23. 23.
    Cunninghame Graham DS, Akil M, Vyse TJ (2007) Association of polymorphisms across the tyrosine kinase gene, TYK2 in UK SLE families. Rheumatology 46:927–930CrossRefGoogle Scholar
  24. 24.
    de Veer MJ, Holko M, Frevel M, Walker E, Der S, Paranjape JM, Silverman RH, Williams BR (2001) Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol 69:912–920PubMedGoogle Scholar
  25. 25.
    Cunninghame Graham DS, Morris DL, Bhangale TR, Criswell LA, Syvänen AC, Rönnblom L, Behrens TW, Graham RR, Vyse TJ (2011) Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. PLoS Genet 7:e1002341CrossRefGoogle Scholar
  26. 26.
    Hellquist A, Jarvinen TM, Koskenmies S, Zucchelli M, Orsmark-Pietras C, Berglind L, Panelius J, Hasan T, Julkunen H, D’Amato M, Saarialho-Kere U, Kere J (2009) Evidence for genetic association and interaction between the TYK2 and IRF5 genes in systemic lupus erythematosus. J Rheumatol 36:1631–1638CrossRefGoogle Scholar
  27. 27.
    Kyogoku C, Morinobu A, Nishimura K, Sugiyama D, Hashimoto H, Tokano Y, Mimori T, Terao C, Matsuda F, Kuno T, Kumagai S (2009) Lack of association between tyrosine kinase 2 (TYK2) gene polymorphisms and susceptibility to SLE in a Japanese population. Mod Rheumatol 19:401–406CrossRefGoogle Scholar
  28. 28.
    Suarez-Gestal M, Calaza M, Endreffy E, Pullmann R, Ordi-Ros J, Sebastiani GD, Ruzickova S, Jose Santos M, Papasteriades C, Marchini M, Skopouli FN, Suarez A, Blanco FJ, D’Alfonso S, Bijl M, Carreira P, Witte T, Migliaresi S, Gomez-Reino JJ, Gonzalez A, European Consortium of SLEDNAC (2009) Replication of recently identified systemic lupus erythematosus genetic associations: a case–control study. Arthritis Res Ther 11:R69CrossRefGoogle Scholar
  29. 29.
    Tang L, Wan P, Wang Y, Pan J, Wang Y, B C (2015) Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population. Inflamm Res 64:817–824CrossRefGoogle Scholar
  30. 30.
    Lee YH, Choi SJ, Ji JD, Song GG (2012) Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis. Inflamm Res 61:949–954CrossRefGoogle Scholar
  31. 31.
    Chong WP, Ip WK, Wong WH, Lau CS, Chan TM, Lau YL (2004) Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus. Genes Immun 5:484–492CrossRefGoogle Scholar
  32. 32.
    Zhou M, Ding L, Peng H, Wang B, Huang F, Xu WD, Li JH, Ye XR, Pan HF, Ye DQ (2013) Association of the interleukin-10 gene polymorphism (−1082A/G) with systemic lupus erythematosus: a meta-analysis. Lupus 22:128–135CrossRefGoogle Scholar
  33. 33.
    Kawasaki M, Fujishiro M, Yamaguchi A, Nozawa K, Kaneko H, Takasaki Y, Takamori K, Ogawa H, Sekigawa I (2011) Possible role of the JAK/STAT pathways in the regulation of T cell-interferon related genes in systemic lupus erythematosus. Lupus 20:1231–1239CrossRefGoogle Scholar
  34. 34.
    Crawley E, Woo P, Isenberg DA (1999) Single nucleotide polymorphic haplotypes of the interleukin-10 5′ flanking region are not associated with renal disease or serology in Caucasian patients with systemic lupus erythematosus. Arthritis Rheum 42:2017–2018CrossRefGoogle Scholar
  35. 35.
    D’ Alfonso S, Giordano M, Mellai M, Lanceni M, Barizzone N, Marchini M, Scorza R, Danieli MG, Cappelli M, Rovere P, Sabbadini MG (2002) Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region. Genes Immun 3:454–463CrossRefGoogle Scholar
  36. 36.
    da Silva HD, da Silva AP, da Silva HA, Asano NM, Maia Mde M, de Souza PR (2014) Interferon gamma and Interleukin 10 polymorphisms in Brazilian patients with systemic lupus erythematosus. Mol Biol Rep 41:2493–2500CrossRefGoogle Scholar
  37. 37.
    Dijstelbloem HM, Hepkema BG, Kallenberg CG, van der Linden MW, Keijsers V, Huizinga TW, Jansen MD, van de Winkel JG (2002) The R-H polymorphism of FCγ receptor IIa as a risk factor for systemic lupus erythematosus is independent of single-nucleotide polymorphisms in the interleukin-10 gene promoter. Arthritis Rheum 46:1125–1126CrossRefGoogle Scholar
  38. 38.
    Fei GZ, Svenungsson E, Frostegård J, Padyukov L (2004) The A-1087IL-10 allele is associated with cardiovascular disease in SLE. Atherosclerosis 177:409–414CrossRefGoogle Scholar
  39. 39.
    Guarnizo-Zuccardi P, Lopez Y, Giraldo M, Garcia N, Rodriguez L, Ramirez L, Uribe O, Garcia L, Vasquez G (2007) Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens 70:376–382CrossRefGoogle Scholar
  40. 40.
    Guzowski D, Chandrasekaran A, Gawel C, Palma J, Koenig J, Wang XP, Dosik M, Kaplan M, Chu CC, Chavan S, Furie R, Albesiano E, Chiorazzi N (2005) Analysis of single nucleotide polymorphisms in the promoter region of interleukin-10 by denaturing high-performance liquid chromatography. J Biomol Tech 16:154–166PubMedPubMedCentralGoogle Scholar
  41. 41.
    Hee CS, Gun SC, Naidu R, Somnath SD, Radhakrishnan AK (2008) The relationship between single nucleotide polymorphisms of the interleukin-10 gene promoter in systemic lupus erythematosus patients in Malaysia: a pilot study. Int J Rheum Dis 11:148–154CrossRefGoogle Scholar
  42. 42.
    Hirankarn N, Wongpiyabovorn J, Hanvivatvong O, Netsawang J, Akkasilpa S, Wongchinsri J, Hanvivadhanakul P, Korkit W, Avihingsanon A (2006) The synergistic effect of FC gamma receptor IIa and interleukin-10 genes on the risk to develop systemic lupus erythematosus in Thai population. Tissue Antigens 68:399–406CrossRefGoogle Scholar
  43. 43.
    Hrycek A, Siekiera U, Cieślik P, Szkróbka W (2005) HLA-DRB1 and-DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus. Rheumatol Int 26:1–6CrossRefGoogle Scholar
  44. 44.
    Khoa PD, Sugiyama T, Yokochi T (2005) Polymorphism of interleukin-10 promoter and tumor necrosis factor receptor II in Vietnamese patients with systemic lupus erythematosus. Clin Rheumatol 24:11–13CrossRefGoogle Scholar
  45. 45.
    Lazarus M, Hajeer AH, Turner D, Sinnott P, Worthington J, Ollier WE, Hutchinson IV (1997) Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus. J Rheumatol 24:2314–2317PubMedGoogle Scholar
  46. 46.
    Lin YJ, Wan L, Huang CM, Sheu JJ, Chen SY, Lin TH, Chen DY, Hsueh KC, Lai CC, Tsai FJ (2010) IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan. Clin Exp Rheumatol 28:318–324PubMedGoogle Scholar
  47. 47.
    Mok CC, Lanchbury JS, Chan DW, Lau CS (1998) Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus. Arthritis Rheum 41:1090–1095CrossRefGoogle Scholar
  48. 48.
    Rezaei A, Ziaee V, Sharabian FT, Harsini S, Mahmoudi M, Soltani S, Sadr M, Moradinejad MH, Aghighi Y, Rezaei N (2015) Lack of association between interleukin-10, transforming growth factor-beta gene polymorphisms and juvenile-onset systemic lupus erythematosus. Clin Rheumatol 34:1059–1064CrossRefGoogle Scholar
  49. 49.
    Rianthavorn P, Chokedeemeeboon C, Deekajorndech T, Suphapeetiporn K (2013) Interleukin-10 promoter polymorphisms and expression in Thai children with juvenile systemic lupus erythematosus. Lupus 22:721–726CrossRefGoogle Scholar
  50. 50.
    Rood MJ, Keijsers V, van der Linden MW, Tong TQ, Borggreve SE, Verweij CL, Breedveld FC, Huizinga TW (1999) Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes. Ann Rheum Dis 58:85–89CrossRefGoogle Scholar
  51. 51.
    Rosado S, Rua-Figueroa I, Vargas JA, Garcia-Laorden MI, Losada-Fernandez I, Martin-Donaire T, Perez-Chacon G, Rodriguez-Gallego C, Naranjo-Hernandez A, Ojeda-Bruno S, Citores MJ (2008) Interleukin-10 promoter polymorphisms in patients with systemic lupus erythematosus from the Canary Islands. Int J Immunogenet 35:235–242CrossRefGoogle Scholar
  52. 52.
    Sobkowiak A, Lianeri M, Wudarski M, Łącki JK, Jagodziński PP (2009) Genetic variation in the interleukin-10 gene promoter in Polish patients with systemic lupus erythematosus. Rheumatol Int 29:921–925CrossRefGoogle Scholar
  53. 53.
    Suárez A, López P, Mozo L, Gutiérrez C (2005) Differential effect of IL10 and TNFα genotypes on determining susceptibility to discoid and systemic lupus erythematosus. Ann Rheum Dis 64:1605–1610CrossRefGoogle Scholar
  54. 54.
    Talaat RM, Alrefaey SA, Bassyouni IH, Ashour ME, Raouf AA (2016) Genetic polymorphisms of interleukin 6 and interleukin 10 in Egyptian patients with systemic lupus erythematosus. Lupus 25:255–264CrossRefGoogle Scholar
  55. 55.
    Van der Linden MW, Westendorp RG, Sturk A, Bergman W, Huizinga TW (2000) High interleukin-10 production in first-degree relatives of patients with generalized but not cutaneous lupus erythematosus. J Investig Med 48:327–334PubMedGoogle Scholar
  56. 56.
    Yu HH, Liu PH, Lin YC, Chen WJ, Lee JH, Wang LC, Yang YH, Chiang B (2010) Interleukin 4 and STAT6 gene polymorphisms are associated with systemic lupus erythematosus in Chinese patients. Lupus 19:1219–1228CrossRefGoogle Scholar
  57. 57.
    Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725CrossRefGoogle Scholar
  58. 58.
    Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24:1291–1306CrossRefGoogle Scholar
  59. 59.
    Liu P, Song J, Su H, Li L, Lu N, Yang R, Peng Z (2013) IL-10 gene polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis. PLoS One 8:e69547CrossRefGoogle Scholar
  60. 60.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefGoogle Scholar
  61. 61.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634CrossRefGoogle Scholar
  62. 62.
    Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M (2007) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Int J Surg 4:1500–1524Google Scholar
  63. 63.
    Molineros JE, Maiti AK, Sun C, Looger LL, Han S, Kim-Howard X, Glenn SAA, Kelly JA, Niewold TB, Gilkeson GS, Brown EE, Alarcón GS, Edberg JC, Petri M, Ramsey-Goldman R, Reveille JD, Vilá LM, Freedman BI, Tsao BP, Criswell LA, Jacob CO, Moore JH, Vyse TJ, Langefeld CL, Guthridge JM, Gaffney PM, Moser KL, Scofield RH, A-R BIOLUPUS Network, Williams SM, Merrill JTJ, Ames JA, Kaufman KM, Kimberly RP, Harley JB (2013) Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production. PLoS Genet 9:e1003222CrossRefGoogle Scholar
  64. 64.
    Cen H, Leng RX, Wang W, Zhou M, Feng CC, Zhu Y, Yang XK, Yang M, Zhai Y, Li BZ, Liu J, Pan HF, Ye DQ (2013) Association study of IFIH1 rs1990760 polymorphism with systemic lupus erythematosus in a Chinese population. Inflammation 36:444–448CrossRefGoogle Scholar
  65. 65.
    Wang C, Ahlford A, Laxman N, Nordmark G, Eloranta ML, Gunnarsson I, Svenungsson E, Padyukov L, Sturfelt G, Jönsen A, Bengtsson AA, Truedsson L, Rantapää-Dahlqvist S, Sjöwall C, Sandling JK, Rönnblom L, Syvänen AC (2013) Contribution of IKBKE and IFIH1 gene variants to SLE susceptibility. Genes Immun 14:217–222CrossRefGoogle Scholar
  66. 66.
    Enevold C, Kjær L, Nielsen CH, Voss A, Jacobsen RS, Hermansen ML, Redder L, Oturai AB, Jensen PE, Bendtzen K, Jacobsen S (2014) Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes. Rheumatol Int 34:1401–1408CrossRefGoogle Scholar
  67. 67.
    Gono T, Kawaguchi Y, Sugiura T, Furuya T, Kawamoto M, Hanaoka M, Yamanaka H (2010) Interferon-induced helicase (IFIH1) polymorphism with systemic lupus erythematosus and dermatomyositis/polymyositis. Mod Rheumatol 20:466–470CrossRefGoogle Scholar
  68. 68.
    Silva JA, Lima SC, Addobbati C, Moura R, Brandão LA, Pancoto JA, Donadi EA, Crovella S, Sandrin-Garcia P (2016) Association of interferon-induced helicase C domain (IFIH1) gene polymorphisms with systemic lupus erythematosus and a relevant updated meta-analysis. Genet Mol Res. CrossRefPubMedGoogle Scholar
  69. 69.
    Li P, Chang YK, SHEK KW, Lau YL (2011) Lack of association of TYK2 gene polymorphisms in Chinese patients with systemic lupus erythematosus. J Rheumatol 38:177–178CrossRefGoogle Scholar
  70. 70.
    Nan S (2003) Variations in the IL-10 promoter region confer susceptibility to systemic lupus erythematosus in Chinese population. [article in chinese]. Shanghai Yi Xue 26:452–459Google Scholar
  71. 71.
    Wang FY, Li GC, Xie HF, Luo QZ, Zha GZ, Ping Y (2007) Polymorphism and SLE in Chinese Han population of Hunan province [article in chinese]. Acta Laser Biol Sin 16:344–348Google Scholar
  72. 72.
    Lan Y, Qin J, Wu J, Tang XS, Qin JM (2007) Association between the polymorphism in interleukin-10 gene promoter and systematic lupus erythematosus in a Chinese Zhuang population in Guangxi Zhuang Nationality Autonomous Region (in chinese). Chin J Dermatol 40:555–557Google Scholar
  73. 73.
    Miteva L, Manolova I, Ivanova M, Stoilov R, Rashkov R (2010) Lack of association between promoter polymorphism – 1082A/G in interleukin-10 gene and genetic predisposition to systemic lupus erythematosus. Revmatologia 18(18):33–38 33–38.Google Scholar
  74. 74.
    Zhou H, Qu R, Tang ZH, Liu Z (2007) Investigation of the correlation between interleukin-10 promoter polymorphisms and systemic lupus erythematosus [article in chinese]. Chin J Dermatol Venereol 21:517–520Google Scholar
  75. 75.
    Lu LY, Cheng HH, Sung PK, Tai MH, Yeh JJ, Chen A (2005) Tumor necrosis factor-beta + 252A polymorphism is associated with systemic lupus erythematosus in Taiwan. J Formosan Med Assoc 104:563–570PubMedGoogle Scholar
  76. 76.
    Ren XY, Li Y, Ren LL, Wang L, Wang YK (2011) The research of genetic association of interleukin-10 polymorphisms with systemic lupus erythematosus [article in chinese]. Guide China Med 9:24–27Google Scholar
  77. 77.
    Lin PW, Huang CM, Huang CC, Tsai CH, Tsai JJ, Chang CP, Tsai FJ (2007) The association of -627 interleukin-10 promoter polymorphism in Chinese patients with systemic lupus erythematosus. Clin Rheumatol 26:298–301CrossRefGoogle Scholar
  78. 78.
    Peng H, Wang W, Zhou M, Li R, Pan HF, Ye DQ (2013) Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus. Clin Rheumatol 32:1255–1266CrossRefGoogle Scholar
  79. 79.
    Wang B, Zhu JM, Fan YG, Xu WD, Cen H, Pan HF, Ye DQ (2013) Association of the—1082G/A polymorphism in the interleukin-10 gene with systemic lupus erythematosus: a meta-analysis. Gene 519:209–216CrossRefGoogle Scholar
  80. 80.
    Goropevšek A, Holcar M, Avčin T (2017) The role of STAT signaling pathways in the pathogenesis of systemic lupus erythematosus. Clin Rev Allergy Immunol 52:164–181CrossRefGoogle Scholar
  81. 81.
    Reineke U, Schneider-Mergener J, Glaser RW, Stigler RD, Seifert M, Volk HD, Sabat R (1999) Evidence for conformationally different states of interleukin-10 binding of a neutralizing antibody enhances accessibility of a hidden epitope. J Mol Recognit 12:242–248CrossRefGoogle Scholar
  82. 82.
    Wolk K, Witte E, Reineke U, Witte K, Friedrich M, Sterry W, Asadullah K, Volk HD, Sabat R (2005) Is there an interaction between interleukin-10 and interleukin-22? Genes Immun 6:8–18CrossRefGoogle Scholar
  83. 83.
    Yoon SI, Logsdon NJ, Sheikh F, Donnelly RP, Walter MR (2006) Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. J Biol Chem 281:35088–35096CrossRefGoogle Scholar
  84. 84.
    Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M, Akira S, Yonehara S, Kato A, Fujita T (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 175:2851–2858CrossRefGoogle Scholar
  85. 85.
    Bentham J, Morris DL, Graham DSC, Pinder CL, Tombleson P, Behrens TW, Martin J, Fairfax BP, Knight JC, Chen L, Replogle J, Syvanen AC, Ronnblom L, Graham RR, Wither JE, Rioux JD, Alarcon-Riquelme ME, Vyse TJ (2015) Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat Genet 47:1457–1464CrossRefGoogle Scholar
  86. 86.
    Cen H, Wang W, Leng RX, Wang TY, Pan HF, Fan YG, Wang B, Ye DQ (2013) Association of IFIH1 rs1990760 polymorphism with susceptibility to autoimmune diseases: a meta-analysis. Autoimmunity 46:455–462CrossRefGoogle Scholar
  87. 87.
    Song GG, Choi SJ, Ji JD, Lee YH (2013) Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis. Hum Immunol 74:364–370CrossRefGoogle Scholar
  88. 88.
    Weber-Nordt RM, Riley JK, Greenlund AC, Moore KW, Darnell JE, Schreiber RD (1996) Stat3 recruitment by two distinct ligand-induced, tyrosine-phosphorylated docking sites in the interleukin-10 receptor intracellular domain. J Biol Chem 271:27954–27961CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Qiong Yin
    • 1
    • 2
  • Liang-Cai Wu
    • 3
  • Lu Zheng
    • 4
  • Ming-Yu Han
    • 5
  • Li-Ya Hu
    • 2
  • Pian-Pian Zhao
    • 1
  • Wei-Yang Bai
    • 1
  • Xiao-Wei Zhu
    • 1
  • Jiang-Wei Xia
    • 1
  • Xiao-Bo Wang
    • 2
  • Xing-Wei Zhang
    • 2
  • Hou-Feng Zheng
    • 1
    • 2
    Email author
  1. 1.Diseases & Population (DaP) Geninfo Lab, School of Life SciencesWestlake University and Westlake Institute for Advanced StudyHangzhouChina
  2. 2.Institute of Aging Research and the Affiliated Hospital, School of MedicineHangzhou Normal UniversityHangzhouChina
  3. 3.Department of Dermatology, The 6th Affiliated HospitalSun Yat-sen UniversityGuangzhouChina
  4. 4.Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanChina
  5. 5.School of Biomolecular and Biomedical ScienceUniversity College DublinDublinIreland

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