FCRL3 gene polymorphisms contribute to the radiographic severity rather than susceptibility of rheumatoid arthritis

The ethnic heterogeneity and genetic complexity of rheumatoid arthritis (RA) have produced inconsistent results in previous genetic association studies concerning FCRL3. This study sought to delineate the association between the FCRL3 gene polymorphisms and susceptibility to RA and to investigate the effects of the polymorphisms on the progression of joint destruction in RA. RA patients (n = 377) and healthy unrelated controls (n = 298) were recruited. Genotyping of -169 T>C and -110 G>A in the promoter and 1,381 G>A in the intron was accomplished using FRET assays. The distribution of genotypes and haplotypes did not differ between RA patients and controls. When we investigated the role of FCRL3 polymorphisms for the severity of RA, patients with the CC genotype in the -169 T>C polymorphism had a higher modified Sharp score than other genotype groups (p = 0.034) among patients with disease duration ≥10 years. The slope of the regression line for modified Sharp score over disease duration (10.12/year) was significantly steeper in patients with the CC genotype than in the T carriers (5.69/year) at the -169 T>C polymorphism (p = 0.003), indicating the faster progression of radiologic destruction in the CC genotype. In conclusion, polymorphisms of the FCRL3 gene may contribute to the progression of joint destruction rather than susceptibility of RA.