Association between interleukin-18 polymorphisms and systemic lupus erythematosus: a meta-analysis
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Association between interleukin-18 polymorphisms and systemic lupus erythematosus: a meta-analysis Gwan Gyu Song • Sung Jae Choi • Jong Dae Ji Young Ho Lee
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Received: 13 June 2012 / Accepted: 9 December 2012 / Published online: 14 December 2012 Ó Springer Science+Business Media Dordrecht 2012
Abstract The aim of this study was to determine whether the three functional interleukin-18 (IL-18) promoter -607 C/A (rs1946518), -137 G/C (rs187238), and -1297 C/T (rs360719) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. Meta-analysis was conducted on the associations between these IL-18 polymorphisms and SLE using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 11 comparisons (nine studies) involving 8,453 subjects (2,928 SLE patients and 5,525 controls) were included in the meta-analysis. In all study subjects, meta-analysis showed no association between SLE and the IL-18 -607 C allele (odds ratio [OR] = 1.065, 95 % confidence interval [CI] = 0.870–1.303, p = 0.541). However, stratification by ethnicity indicated a significant association between this allele and SLE in Europeans (OR = 0.864, 95 % CI = 0.757–0.986, p = 0.031), but not in Asians (OR = 1.230, 95 % CI = 0.902–1.676, p = 0.190). Metaanalyses showed the same pattern for the IL-18 -607 C allele using the dominant and additive models. Metaanalysis of the IL-18 -137 G/C polymorphism showed no association between SLE and the IL-18 -137 G allele in all study subjects (OR = 0.916, 95 % CI = 0.836–1.003, p = 0.057), but stratification by ethnicity indicated a significant association between this allele and SLE in Asians (OR = 0.792, 95 % CI = 0.629–0.997, p = 0.047), but not in Europeans (OR = 0.930, 95 % CI = 0.839–1.032,
G. G. Song S. J. Choi J. D. Ji Y. H. Lee (&) Division of Rheumatology, Department of Internal Medicine Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Korea e-mail: [email protected]
p = 0.171). Furthermore, meta-analysis showed that the IL-18 -1297 C allele was significantly associated with SLE in all study subjects and in Europeans (OR = 1.240, 95 % CI = 1.052–1.482, p = 0.010 and OR = 1.303, 95 % CI = 1.050–1.617, p = 0.016). This meta-analysis shows that the IL-18 -607 C/A and -1297 C/T polymorphism are associated with the development of SLE in Europeans, and the IL-18 -137 G/C polymorphism is associated with SLE in Asians. Keywords Interleukin-18 Polymorphism Systemic lupus erythematosus Meta-analysis
Introduction Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease, which is characterized by intense inflammation and multiple organ damage. Furthermore, significant familial aggregation, convincing demonstrations of multiple genetic linkages, and its associations demonstrate that the etiology of SLE is genetic in nature [1, 2]. Interleukin-18 (IL-18), which was initially described as an IFN-c-inducing factor in T cel
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