Association between interleukin-18 polymorphisms and systemic lupus erythematosus: a meta-analysis

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). Meta-analyses showed the same pattern for the IL-18 -607 C allele using the dominant and additive models. Meta-analysis 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, 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.