Abstract
BackgroundRheumatoid arthritis (RA) is the most common autoimmune system diseases in our world. More studies in recent years have shown that FCRL gene polymorphisms is closely related to autoimmune diseases. It is suggested that genetic factors play a crucial role in the pathogenesis of this disease. In this study, we aimed to investigate the relationship between FCRL1 rs2050568, FCRL3 rs2317230 and FCRL6 rs58240276 polymorphisms and RA risk in the Chinese Han population. 506 with RA patients and 509 healthy controls were recruited in this study, and the single nucleotide polymorphisms (SNPs) was successfully genotyped using the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for age and gender were conducted to assess these SNPs polymorphisms and RA risk. The multifactor dimensionality reduction (MDR) method was conducted to analyze SNP-SNP interaction.ResultsOur results revealed that there no significant association was observed between the allele and genotype frequencies among these SNPs and RA risk (all p > 0.05). Straified analysis by age and gender, the results confirmed that FCRL1 rs2050568 T/T genotype enhanced the risk of RA in females (p = 0.014). The G/T - T/T genotype of FCRL3 rs2317230 was correlated with a decreased RA risk in males (p = 0.021). We also observed that the C/T-T/T genotype of FCRL6 rs58240276 was increased the risk of RA in the group at age > 54 years (p = 0.016). In addition, FCRL1 rs2050568-TT, FCRL6 rs58240276-TT and FCRL1 rs2050568-TT, FCRL3 rs2317230-TT, FCRL6 rs58240276-TT are the best models for multi-site MDR analysis (p < 0.05), and the two best models mentioned above and classes RA have the most significant correlation.ConclusionsOur study demonstrated that FCRL1 rs2050568, FCRL3 rs2317230, and FCRL6 rs58240276 polymorphisms were correlated with RA susceptibility in the Chinese Han population.
Highlights
Rheumatoid arthritis (RA) one of the most concerning inflammatory diseases with its frequency, chronicity, and system characterized by synovial destruction and joint inflammation, which leads to reduce the quality of life and even causes to the disability [1, 2]
Stratification analysis on the association between Single nucleotide polymorphism (SNP) and RA risk When the stratification analysis by age was conducted, the results suggested that the C/T – T/T genotype of FCRL6 rs58240276 polymorphism was significant increased the risk of RA in the old group at age > 54 years in under the dominant model (OR = 1.54, 95% Confidence interval (CI) = 1.08–2.19, p = 0.016)
Our results confirmed that FCRL1 rs2050568 T/ T genotype enhanced the risk of RA in females under the recessive model (OR = 1.64, 95% confidence intervals (95% CIs) = 1.10–2.45, p = 0.014)
Summary
Rheumatoid arthritis (RA) one of the most concerning inflammatory diseases with its frequency, chronicity, and system characterized by synovial destruction and joint inflammation, which leads to reduce the quality of life and even causes to the disability [1, 2]. Increasing genomewide association studies (GWAS) have been identified more than hundreds of single-nucleotide polymorphisms (SNPs) correlated with autoimmune diseases, such as ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and RA [6,7,8]. Fc receptor-like (FCRL) gene family a new member of the Ig superfamily, which encodes the protein may play an essential role in regulating B signaling [9]. The T/G genotype of FCRL3 rs2317230 polymorphism significantly increased the risk of RA in the European and Asian populations (OR = 1.07, 95% CI = 1.04– 1.10, p = 1.0E-05, OR = 1.10, 95%CI = 1.04–1.16, p = 3.1E-04, respectively). The FCRL3 rs2317230 polymorphism is associated with the risk of RA in the Europeans and Asians populations. More studies in recent years have shown that FCRL gene polymorphisms is closely related to autoimmune diseases. The multifactor dimensionality reduction (MDR) method was conducted to analyze SNP-SNP interaction
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