THU0037 ASSOCIATION BETWEEN PRO-INFLAMMATORY CYTOKINE POLYMORPHISMS AND JUVENILE IDIOPATHIC ARTHRITIS
Authors: Jae Hyun Jung, Jae-Hoon Kim, Sung Jae Choi, Gwan Gyu Song
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is the most common chronic arthritis of childhood and has a variety of subtypes, but the etiology is unclear. Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α play a major role in the development of JIA. Single nucleotide polymorphisms (SNPs) may be associated with susceptibility, phenotype, progression, and treatment of JIA, and the relevance of more than 20 SNPs and JIA has been studied. <h3>Objectives</h3> We investigated whether IL-1, IL-6, and TNF-α polymorphisms were associated with susceptibility to JIA. <h3>Methods</h3> A meta-analysis was conducted on the associations between IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA. A literature search was performed using PubMed and Embase. The strength of the association between these cytokine polymorphisms and risk of JIA was estimated using the crude odds ratio (OR) and 95% confidential interval (CI). We performed meta-analyses using 1) allelic contrast, 2) recessive, 3) dominant, and 4) additive models. The heterogeneity between studies was assessed with the Cochran Q test, and the heterogeneity among studies was tested with the <i>I</i>² statistic. <h3>Results</h3> A total of 27 studies included 4,678 JIA cases and 7,634 control subjects. There were 23 studies on Caucasians, 3 on Asians, and 1 on Africans. Seven studies were on IL-1α-899 C/T, 5 were on IL-1β-511 C/T, 6 were on IL-6-174 G/C, 19 were on TNF-α-308 G/A, and 14 were on TNF-α -238 G/A polymorphisms. Meta-analysis of IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms revealed no significant associations between JIA and minor alleles (OR 0.99, 95% CI 0.87–1.12, <i>P</i> =0.84; OR 1.10, 95% CI 0.97–1.25, <i>P</i> =0.15; OR 1.04, 95% CI 0.91–1.19, <i>P</i> =0.57; OR 1.09, 95% CI 0.87–1.37, <i>P</i> =0.46; OR 0.85, 95% CI 0.63–1.13, <i>P</i> =0.26). Subgroup analysis was conducted on the relationship between JIA and proinflammatory cytokines based on ethnicity. In Caucasians, there was no significant association between IL-1α-899 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms and JIA; however, there were significant relationships between JIA and recessive (TT vs. CT + CC) and additive (TT vs. CC) models of IL-1β-511 C/T polymorphisms (OR 1.48, 95% CI 1.09–2.00, <i>P</i> =0.01; OR 1.46, 95% CI 1.05–2.03, <i>P</i> =0.02). <h3>Conclusion</h3> IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms were not significantly associated with overall JIA susceptibility in all ethnicities. However, differences according to ethnicity were observed, and the TT genotype of IL-1β-511 C/T was associated with a high prevalence of JIA in Caucasians. <h3>References</h3> [1] Cimaz R, Cazalis MA, Reynaud C, Gerloni V, Zulian F, Biggioggero M, Martini G, Pontikaki I, Fantini F, Mougin B, Miossec P (2007) IL1 and TNF gene polymorphisms in patients with juvenile idiopathic arthritis treated with TNF inhibitors. Ann Rheum Dis 66:900-904. [2] Donn RP, Barrett JH, Farhan A, Stopford A, Pepper L, Shelley E, Davies N, Ollier WER, Thomson W (2001) Cytokine gene polymorphisms and susceptibility to juvenile idiopathic arthritis. British Paediatric Rheumatology Study Group. Arthritis Rheum 44:802-810. [3] McDowell TL, Symons JA, Ploski R, Førre Ø, Duff GW (1995) A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1α polymorphism. Arthritis Rheumatism 38:221-228. <h3>Acknowledgement</h3> No grant or other support was received for this study. <h3>Disclosure of Interests</h3> None declared