Background A number of observational studies have been conducted to investigate the association of the IL-10 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility. However, their results are conflicting. Method We searched published case-control studies on the IL-10 polymorphisms and SLE in PubMed, EMBASE and Chinese Biomedical Literature Database. A meta-analysis was conducted using a fixed-effect or random-effect model based on between-study heterogeneity. Results A total of 42 studies with 7948 cases and 11866 controls were included in this meta-analysis. Among Caucasians, the CA27 allele of the IL10.G microsatellites (OR 2.38, 95% CI 1.01–5.62), the G allele of the IL-10 -1082G/A polymorphism (G vs. A: OR 1.21, 95% CI 1.02–1.44; GG vs. AA: OR 1.45, 95% CI 1.16–1.82; GG+GA vs. AA: OR 1.16, 95% CI 1.03–1.29) and its associated haplotype -1082G/？819C/？592C (OR 1.25, 95% CI 1.10–1.42) were associated with increased SLE susceptibility without or with unimportant between-study heterogeneity. Removing studies deviating from Hardy-Weinberg equilibrium (HWE) hardly changed these results. Among Asians, the CA21 allele of the IL-10.G microsatellites (OR 1.28, 95% CI 1.02–1.60) and the -1082G/？819C/？592C haplotype (OR 1.24, 95% CI 1.00–1.53) were associated with increased SLE susceptibility, but with substantial between-study heterogeneity or sensitive to HWE status. Removing studies deviating from HWE also produced statistically significant associations of the IL-10 -1082G/A (GG vs. AA: OR 3.21, 95% CI 1.24–8.28; GG vs. AA+GA: OR 2.85, 95% CI 1.19–6.79) and -592C/A polymorphisms (CC+CA vs. AA: OR 0.69, 95% CI 0.51–0.94) with SLE among Asians. Conclusion This meta-analysis showed that the IL10.G microsatellites, the IL-10 -1082G/A and -592C/A polymorphisms and the haplotype -1082G/？819C/？592C are associated with SLE susceptibility. Besides, this is the first time to report an association between the CA27 allele of the IL-10.G microsatellites and SLE among Caucasians. Further studies are needed to confirm these findings.
References
[1]
Tsokos GC (2011) Systemic lupus erythematosus. N Engl J Med 365: 2110–2121.
Danchenko N, Satia JA, Anthony MS (2006) Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 15: 308–318.
[4]
Alarcon-Riquelme ME (2002) Family studies in systemic lupus erythematosus. Rheumatology (Oxford) 41: 364–366.
[5]
Sullivan KE (2000) Genetics of systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am 26: 229–256, v–vi.
[6]
Llorente L, Zou W, Levy Y, Richaud-Patin Y, Wijdenes J, et al. (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181: 839–844.
[7]
Rousset F, Garcia E, Defrance T, Peronne C, Vezzio N, et al. (1992) Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A 89: 1890–1893.
[8]
de Waal Malefyt R, Yssel H, de Vries JE (1993) Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J Immunol 150: 4754–4765.
[9]
Taga K, Tosato G (1992) IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol 148: 1143–1148.
[10]
Hagiwara E, Gourley MF, Lee S, Klinman DK (1996) Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10:interferon-gamma-secretin？gcells in the peripheral blood. Arthritis Rheum 39: 379–385.
[11]
Horwitz DA, Gray JD, Behrendsen SC, Kubin M, Rengaraju M, et al. (1998) Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus. Arthritis Rheum 41: 838–844.
[12]
Houssiau FA, Lefebvre C, Vanden Berghe M, Lambert M, Devogelaer JP, et al. (1995) Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity. Lupus 4: 393–395.
[13]
Lacki JK, Samborski W, Mackiewicz SH (1997) Interleukin-10 and interleukin-6 in lupus erythematosus and rheumatoid arthritis, correlations with acute phase proteins. Clin Rheumatol 16: 275–278.
[14]
Llorente L, Richaud-Patin Y, Fior R, Alcocer-Varela J, Wijdenes J, et al. (1994) In vivo production of interleukin-10 by non-T cells in rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. A potential mechanism of B lymphocyte hyperactivity and autoimmunity. Arthritis Rheum 37: 1647–1655.
[15]
Llorente L, Richaud-Patin Y, Wijdenes J, Alcocer-Varela J, Maillot MC, et al. (1993) Spontaneous production of interleukin-10 by B lymphocytes and monocytes in systemic lupus erythematosus. Eur Cytokine Netw 4: 421–427.
[16]
Park YB, Lee SK, Kim DS, Lee J, Lee CH, et al. (1998) Elevated interleukin-10 levels correlated with disease activity in systemic lupus erythematosus. Clin Exp Rheumatol 16: 283–288.
[17]
Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, et al. (1994) Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 179: 305–310.
[18]
Lauwerys BR, Garot N, Renauld JC, Houssiau FA (2000) Interleukin-10 blockade corrects impaired in vitro cellular immune responses of systemic lupus erythematosus patients. Arthritis Rheum 43: 1976–1981.
[19]
Llorente L, Richaud-Patin Y, Garcia-Padilla C, Claret E, Jakez-Ocampo J, et al. (2000) Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 43: 1790–1800.
[20]
Iyer SS, Cheng G (2012) Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol 32: 23–63.
[21]
Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315: 1533–1537.
[22]
Yu Y, Wang W, Zhai S, Dang S, Sun M (2012) IL6 gene polymorphisms and susceptibility to colorectal cancer: a meta-analysis and review. Mol Biol Rep 39: 8457–8463.
[23]
Dang SS, Wang WJ, Wang XF, Li YP, Li M, et al. (2012) Telaprevir for chronic hepatitis C with genotype 1: a meta-analysis. Hepatogastroenterology 59: 461–468.
[24]
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719–748.
[25]
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177–188.
[26]
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315: 629–634.
[27]
Lazarus M, Hajeer AH, Turner D, Sinnott P, Worthington J, et al. (1997) Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus. J Rheumatol 24: 2314–2317.
[28]
Zhou H, Qu R, Tang ZH, Liu C (2007) Investigation of the correlation between interleukin-10 promoter polymorphisms and systemic lupus erythematosus. Chinese Journal of Dermatology and Venereology (in Chineses) 21: 517–520.
[29]
Shen N (2003) Variations in the IL -10 promoter region confer susceptibility to systemic lupus erythematosus in Chinese population. Shanghai Yi Xue (in Chineses) 26: 452–459.
[30]
Lin YJ, Wan L, Huang CM, Sheu JJ, Chen SY, et al. (2010) IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan. Clin Exp Rheumatol 28: 318–324.
[31]
Lu LY, Cheng HH, Sung PK, Tai MH, Yeh JJ, et al. (2005) Tumor necrosis factor-beta +252A polymorphism is associated with systemic lupus erythematosus in Taiwan. J Formos Med Assoc 104: 563–570.
[32]
Wang FY, Li GC, Xie HF, Luo QZ, Zha GZ, et al. (2007) Polymorphism and SLE in Chinese Han population of Hunan province. Acta Laser Biology Sinica (in Chinese) 16: 344–348.
[33]
Chong WP, Ip WK, Wong WH, Lau CS, Chan TM, et al. (2004) Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus. Genes Immun 5: 484–492.
[34]
Guarnizo-Zuccardi P, Lopez Y, Giraldo M, Garcia N, Rodriguez L, et al. (2007) Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens 70: 376–382.
[35]
Sobkowiak A, Lianeri M, Wudarski M, Lacki JK, Jagodzinski PP (2009) Genetic variation in the interleukin-10 gene promoter in Polish patients with systemic lupus erythematosus. Rheumatol Int 29: 921–925.
[36]
Groux H, Cottrez F (2003) The complex role of interleukin-10 in autoimmunity. J Autoimmun 20: 281–285.
[37]
Nath SK, Harley JB, Lee YH (2005) Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis. Hum Genet 118: 225–234.
[38]
Ou TT, Tsai WC, Chen CJ, Chang JG, Yen JH, et al. (1998) Genetic analysis of interleukin-10 promoter region in patients with systemic lupus erythematosus in Taiwan. Kaohsiung J Med Sci 14: 599–606.
[39]
Schotte H, Gaubitz M, Willeke P, Tidow N, Assmann G, et al. (2004) Interleukin-10 promoter microsatellite polymorphisms in systemic lupus erythematosus: association with the anti-Sm immune response. Rheumatology 43: 1357–1363.
[40]
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: 364–370.
[41]
Zhou M, Ding L, Peng H, Wang B, Huang F, et al. (2013) Association of the interleukin-10 gene polymorphism (-1082A/G) with systemic lupus erythematosus: a meta-analysis. Lupus 22: 128–135.
[42]
Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, et al. (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24: 1–8.
[43]
Rees LE, Wood NA, Gillespie KM, Lai KN, Gaston K, et al. (2002) The interleukin-10–1082 G/A polymorphism: allele frequency in different populations and functional significance. Cell Mol Life Sci 59: 560–569.
[44]
Hirankarn N, Wongpiyabovorn J, Hanvivatvong O, Netsawang J, Akkasilpa S, et al. (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: 399–406.
[45]
Yu HH, Liu PH, Lin YC, Chen WJ, Lee JH, et al. (2010) Interleukin 4 and STAT6 gene polymorphisms are associated with systemic lupus erythematosus in Chinese patients. Lupus 19: 1219–1228.
[46]
Eskdale J, Keijsers V, Huizinga T, Gallagher G (1999) Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus. Genes Immun 1: 151–155.
[47]
Temple SE, Lim E, Cheong KY, Almeida CA, Price P, et al. (2003) Alleles carried at positions -819 and -592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae. Immunogenetics 55: 629–632.
[48]
Claudino M, Trombone AP, Cardoso CR, Ferreira SB Jr, Martins W Jr, et al. (2008) The broad effects of the functional IL-10 promoter-592 polymorphism: modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome. J Leukoc Biol 84: 1565–1573.
[49]
Kurreeman FA, Schonkeren JJ, Heijmans BT, Toes RE, Huizinga TW (2004) Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level. Hum Mol Genet 13: 1755–1762.
[50]
Torres-Poveda K, Burguete-Garcia AI, Cruz M, Martinez-Nava GA, Bahena-Roman M, et al. (2012) The SNP at -592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development. Infect Agent Cancer 7: 32.
[51]
Little J, Higgins J (2006) The HuGENet？ HuGE Review Handbook, version 1.0. Avalaible: http://wwwcdcgov/genomics/hugenet/partic？ipatehtm Accessed 1 September 2012.
[52]
Rood MJ, Keijsers V, van der Linden MW, Tong TQ, Borggreve SE, et al. (1999) Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes. Ann Rheum Dis 58: 85–89.
[53]
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: 327–334.
[54]
Attia J, Thakkinstian A, D'Este C (2003) Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol 56: 297–303.
[55]
Pan Z, Trikalinos TA, Kavvoura FK, Lau J, Ioannidis JP (2005) Local literature bias in genetic epidemiology: an empirical evaluation of the Chinese literature. PLoS Med 2: e334.
