Association Of IL-41 Expression Level And Its Single Nucleotide Polymorphisms With Rheumatoid Arthritis

ObjectiveRheumatoid arthritis（RA）is a common autoimmune disease characterized with erosive and symmetrical polyarthritis,which can lead to joint deformities and seriously affect the quality of life of patients.The exact pathogenesis is still unknown.As a newly discovered inflammatory and immune cytokine,IL-41 has been shown to play a role in the inflammatory immune response of autoimmune diseases.This study aims to explore the correlation between expression level of IL-41 and its coding gene METRNL gene single nucleotide polymorphisms（SNPs）with RA.MethodsA case-control study was adopted in this study.A total of 457 RA patients and 544healthy controls were included.For the genotyping part,SNPscan^TMgenotyping technique was used to identify the nine candidate SNPs sites（rs148650224,rs56848030,rs58633906,rs6416856,rs7207886,rs7406561,rs7502145,rs11359166 and rs79856013）of IL-41 coding gene METRNL and analyzing the genetic susceptibility to RA as well as clinical manifestations.For the expressing level part,enzyme linked immunosorbent assay（ELISA）was performed to detect the plasma levels of IL-41,IL-6 and TNF-αin 97RA patients and plasma levels of IL-41 in 101 healthy controls.Meanwhile,correlation between level of IL-41 and its genotype,clinical features of RA as well as proinflammatory cytokines in RA patients were investigated.Results（1）No significant difference was observed between plasma level of IL-41 in RA patients and healthy controls（z=-1.105,P=0.269）.In RA patients,plasma level of IL-41was positively correlated with the expression levels of IL-6 and TNF-α（r_s=0.238,P=0.019;r_s=0.337,P=0.001）;was positively correlated ESR and hs-CRP as well（r_s=0.317,P=0.002;r_s=0.241,P=0.017）;while was negatively correlated with Hb and PLT（r_s=-0.314,P=0.002;r_s=-0.220,P=0.030）;There was no statistical significance between level of IL-41 and BMI,disease duration,RF,anti-CCP antibody,and DAS28 of RA patients（all P>0.05）.（2）The genotypes and alleles distribution of nine SNPs（rs148650224,rs56848030,rs58633906,rs6416856,rs7207886,rs7406561,rs7502145,rs113591666 and rs79856013）of METRNL gene showed no significant difference between RA group and healthy control group（all P>0.05）;and in different genetic models,such as explicit model,implicit model and additive model,no statistical difference existed between the two groups（P>0.05）.Among the CC,TC and TT genotypes of rs7406561,there were significant differences in RF levels between CC and TC genotypes（P<0.05）,but no significant difference existed in the analysis of disease duration,ESR,hs-CRP,anti-CCP and DAS28（all P>0.05）.There was no significant difference in the analysis of disease duration,ESR,hs-CRP,anti-CCP and DAS28 among different genotypes of other eight candidate loci,rs148650224,rs56848030,rs58633906,rs6416856,rs7207886,rs7502145,rs113591666 and rs79856013（all P>0.05）.No correlation was found between plasma level of IL-41 and 9 loci in RA（P>0.05）.ConclusionThe polymorphisms of rs148650224,rs56848030,rs58633906,rs6416856,rs7207886,rs7406561,rs7502145,rs113591666 and rs79856013 of METRNL gene were not statistically associated with the genetic susceptibility of RA,nor were they associated with plasma level of IL-41 and clinical parameters.However,polymorphism of rs7406561 was correlated with RF in RA patients.