In the present study, IL-18 rs1946518 and rs187238 polymorphisms in promoter region was investigated the association with AS susceptibility in Chinese Han population. The results showed that TT genotype of rs1946518 was significantly associated with the elevated risk of AS and T allele was also significantly higher frequency in AS patients than that of the controls, so rs1946518 was the risk factor of AS. But rs187238 didn’t show any significant association with AS occurrence risk in genotype or allele and it was not an independent susceptible factor to AS. In addition, the strong linkage disequilibrium was found between the two polymorphisms and the carriage of rs1946518T-rs187238C haplotype contributed to the risk of AS in this study population. This study is the first time to reveal the impact of IL-18 polymorphisms on AS occurrence risk in Chinese population.
IL-18 is firstly found to induce T helper type 1 (Th1) and NK cells produce IFN-γ. Its precursor protein in humans consists of 193 amino acids without signal peptide and biological activity. IL-18 is a novel cytokine with the similar structure of IL-1 and the analogous biological function of IL-12 . Inactive IL-18 protein is cleaved by Caspase-1 to acquire activity and Caspase-1 has been found to regulate autoinflammation in the occurrence of rheumatic diseases, including AS . In publication, IL-18 can facilitate Th1 cells to secret a number of cytokines, including IFN-γ, IL-2, GM-CSF and so on, and promote the proliferation of Th1 cells, too . However, the balance level of Th1/Th2 cytokines play the key role in AS [20, 21].
Moreover, as a kind of proinflammatory cytokine, IL-18 is recently found to act on articular hondrocytes and synovial tissues, regulate some cell response and participate in joint inflammation and damage . For example, IL-18 gene promoter (-607A/C and − 137C/G) polymorphisms are explored the role in RA based on a meta-analysis, the results show that − 607A/C polymorphism may contribute to the risk of RA . But the relative studies referring to IL-18 and AS are few. Fortunately, published article records that serum IL-18 level in AS patients is obviously higher than that of the controls . IL-18 is also significantly associated with ESR, CRP, BASFI and BASMI which are as indicators of disease activity for AS , and also shows the positive association with TNF-α level in AS. We guess that IL-18 level not only reflects disease activity of AS patients, but participants in regulating some inflammatory cytokines expression such as TNF-α so as to affect AS development. Another article speculates that increased IL-18 induce Th1 proliferation to produce more IFN-γ, which leads to the imbalance of Th1/Th2 and damaged cytokine network, and then the accumulation of adverse factors causes AS.
It is useful to explore the association of gene polymorphisms with disease for early diagnosis and pathogenesis explanation. IL-18 encoding gene IL-18 contains 6 exons and 5 introns and have been discovered a number of SNPs, which rs1946518 and rs187238 in promoter region are the most common SNPs in IL-18. rs1946518 (-607G/T) have been reported to be associated with promoter activity  and it may alter the expression of IL-18 mRNA to cause a series of pathological changes in body and involves in AS etiology. Rs187238 is the another functional polymorphism which affects transcriptional activity of IL-18 . However, so far, no study reports the association of IL-18 poymorpisms with AS. So this study is necessary and meaningful.