Association Of The Polymorphisms Of IL-23R Gene With Rheumatoid Arthritis In Sichuan Han Population

Objective: To investigate the association of the four single nucleotide polymorphisms(SNPs)( rs1004819, rs7517847, rs10489629, rs2201841) in interleukin-23 receptor(IL-23R) gene with rheumatoid arthritis(RA) and clinical indicators in Sichuan Han population. Meanwhile, to futher elucidate the role of IL-23 R in the RA pathogenesis from the perspective of genetics.Methods: A total of 192 RA patients and 192 healthy controls were genotyped by single base extension(SBE) method.The genotype and allele frequencies were calculated.The RA patients were stratificated by rheumatoid factor(RF) and anti-citrullinated peptide antibody(ACPA),and the association of IL-23 R gene polymorphisms with RA clinical subtypes was further explored. At the same time, the gender, age, erythrocyte sedimentation rate(ESR), c-reactive protein(CRP), disease activity 28 score(DAS28) and other indicators were compared between the different genotypes. Linkage disequilibrium(LD) and haplotypes were reconstructed and analysed using the Haploview 4.2 program.Results: The results showed that the four analyzed IL-23 R genetic variants were in accordance with the Hardy-Weinberg equilibrium for both groups. The frequencies of the rs10489629 GG genotype and G allele in RA patients were significantly increased compared with the control group(P=0.027,OR 1.68,95%CI:1.09 to 2.61;P=0.006,OR 1.55,95%CI:1.11 to 2.17, respectively). The difference of the frequencies of the rs10489629 G allele in RA patients with positive RF and ACPA was also significant compared with the control group(P=0.002,OR 1.59, 95%CI: 1.17 to 2.18;P=0.032,OR 1.68,95%CI:1.21 to 2.46, respectively). No differences were found in gender, age, ESR, CRP, DAS28 among different genotypes of these 4 SNPs. A significantly highter proportion of CTAC haplotype was noted in healthy control group(PC=0.001,OR 0.27,95%CI:0.16 to 0.47) and a significantly higher proportion of CGGT haplotype was noted in RA patients(PC=0.014,OR 3.27, 95%CI:1.52 to 7.04). No statistical difference was found between RA patients and control group with regard to the other haplotypes(PC>0.05).Conclusion:1.IL-23 R gene polymorphism rs10489629 may be associated with susceptibility to RA in Sichuan Han population and GG genotype and G allele may be the risk factors for developing RA.2.IL-23 R gene polymorphism rs10489629 may be associated with susceptibility to RF+RA and ACPA+RA, and G allele may be the risk factors for the above two different clinical subtypes.3.No significant differences were found in gender, age, ESR, CRP and DAS28 among different genotypes of the 4 SNPs.4. Haplotype CTAC was protective in RA, while haplotype CGGT may be a risk factor for developing RA.