FRI0022 THE ANALYSIS OF THE INVOLVEMENT OF TRANSFORMING-GROWTH INTERACTING FACTOR POLYMORPHISMS IN THE BONE METABOLISM OF RHEUMATOID ARTHRITIS

Background: Rheumatoid arthritis (RA) is an autoimmune disease that mainly invades synovial membranes and further damage to articular cartilage and bone. The abnormal activation of transforming-growth factor β (TGF-β) in the subchondral bone is related to the onset of RA joint cartilage degeneration and transforming-growth interacting factor (TGIF) is a negative regulator of TGF-β signaling, while there is no literature addressing the relationship between TGIF polymorphisms and the bone metabolism of RA. Objectives: The aim of the study was to comprehensively explore the possible association for single nucleotide polymorphisms (SNPs) in the TGIF gene with serum bone metabolism markers and RA susceptibility. Methods: Three SNPs within the TGIF gene were genotyped in 155 RA patients and 168 healthy controls by high resolution melting (HRM) analysis in a case-control study. The serum levels of osteocalcin, bone alkaline phosphatase (BALP) and β type I collagen-crosslinked C telopeptide (β-CTX) were detected by electrochemical luminescence in 108 RA patients randomly selected from RA patients group. Results: Genotypes and alleles frequency analysis showed rs7362020 was associated with bone erosion in RA (P=0.012, P=0.003, respectively) and individuals carrying T allele for rs7362020 showed a decreased RA risk (OR=0.59, 95% CI = 0.42-0.84; P= 0.003). In the gender-specific analysis, rs73620203 polymorphism was associated with bone erosion of female RA patients (P values of the distribution of genotypes and alleles were 0.022 and 0.006, respectively). In addition, RA patients with CC, CT and TT genotypes at rs73620203 locus had statistically significant differences in serum osteocalcin and BALP (P=0.006, P=0.037, respectively) and the serum levels in TT genotype RA patients were significantly lower than CC and CT genotype RA patients. The serum levels of β-CTX in rs85440 AA genotype male RA patients were significantly higher than female RA patients (P=0.001), while the serum levels of osteocalcin and BALP in genotype AA, AG and GG female and male RA patients were not significantly different (P all>0.05). Conclusion: Our study provided the first evidence that rs73620203 is associated with bone erosion of RA and provided new insight into the relationship between three SNPs within TGIF gene and regulation of bone metabolism in RA patients of different genders. Acknowledgments: This work was supported by the National Natural Science Foundation of China (Nos. 81772258) and Science and Technology Agency of Sichuan Province (Nos. 2019YFS0310, 2018FZ0106). Disclosure of Interests: None declared