Association of IL-18 promoter gene polymorphisms with rheumatoid arthritis: a meta-analysis.

Interleukin-18(IL-18) plays a potential pathological role in rheumatoid arthritis (RA). The conclusions of the published reports on the relationship between single-nucleotide polymorphisms -607C/A (rs1946518) and -137G/C (rs187238) located in the IL-18 gene promoter and RA risk remain controversial. This meta-analysis was performed to evaluate the association between IL-18 gene promoter (-607A/C and -137C/G) polymorphisms and RA using (1) allele, (2) codominant, (3) dominant, and (4) recessive models. Literature search was conducted up to January, 2013, in PubMed, EMBASE, Spring-link, Web of Science, Wanfang (Chinese) and China National Knowledge Infrastructure (CNKI). A total of 10 studies from eight articles involving 2,662 cases and 2,168 controls for -607A/C polymorphism and 9 studies from six articles involving 1,331 cases and 1,468 controls for -137C/G polymorphism were considered in the meta-analysis. For the relationship of IL-18 -607A/C polymorphism with RA risk, significant association was observed in allele model (OR = 0.778, 95 % CI = 0.633-0.955) and dominant model (OR = 0.618, 95 % CI = 0.466-0.819). However, no significant association could be observed between -137C/G polymorphism and RA risk under all genetic models (allele model: OR = 0.940, 95 % CI = 0.777-1.138; codominant model: OR = 1.079, 95 % CI = 0.574-2.029; dominant model: OR = 0.913, 95 % CI = 0.779-1.069; recessive model: OR = 1.133, 95 % CI = 0.586-2.190). In the subgroup analysis by ethnicity, significant result was also found in Asian populations but not found in Caucasian populations for the relationship of IL-18 -607A/C polymorphism with RA risk; while no obvious association was found between IL-18 -137C/G polymorphism and RA risk. This meta-analysis indicates that IL-18 -607A/C polymorphism in promoter region may be associated with RA risk.