IL-17, IL-21 and IL-22 polymorphisms in rheumatoid arthritis: A systematic review and meta-analysis

Rheumatoid Arthritis (RA) is an autoimmune systemic disease and in its pathogenesis participate several proinflammatory cytokines, including those produced by Th17 cells. We performed a systematic review aiming to assess the associations between polymorphisms in Th17 cytokines, namely IL-17A, IL-17F, IL-21 and IL-22, and susceptibility to RA.

We searched three electronic databases (MEDLINE, Scopus and Web of Science) for observational studies assessing the association between susceptibility to RA (or its clinical presentation) and polymorphisms of the cytokines IL-17A, IL-17F, IL-21 and IL-22. From the selected studies, we extracted information on the studied polymorphisms, assessed outcomes, and demographic characteristics of participants. We performed random effects meta-analyses assessing the associations between susceptibility to RA and different genotypes of the IL-17A rs2275913, IL-17Frs763780 andIL-17Frs2397084polymorphisms. Primary studies' quality was assessed using the Q-Genie tool.

Fifteen studies were included in this systematic review. Five IL-17A polymorphisms were reported to be associated with susceptibility to RA. For the IL-17A rs2275913 polymorphism, our meta-analysis showed the AA genotype to be significantly associated with lower susceptibility to RA(OR = 0.76; 95%CI = 0.61-0.93;p = 0.01), while the opposite was observed for the GG genotype (OR = 1.20; 95%CI = 1.06-1.35;p = 0.01). Concerning IL-17Frs763780 polymorphism, theTT genotype was found to be significantly less frequent in RA patients(OR = 0.49; 95%CI = 0.31-0.77;p = 0.002), while the opposite was observed for the CT genotype (OR = 2.00; 95%CI = 1.03-3.87;p = 0.04). No significant associations were found regarding rs2397084polymorphisms. For IL-21, rs6822844 and rs4505848 were described to have significant associations with susceptibility to RA. No studies were found assessing IL-22 polymorphisms in RA.

IL-17A rs2275913 and IL-17F rs763780 polymorphisms are significantly associated with susceptibility to RA and with different clinical characteristics of this disease.