Jihye Kim1, Yeon-Kyung Lee2, Youngho Park3, Ayeong Kwon4, Young-Chang Kwon1, Young Bin Joo2, Hye-Soon Lee5, Kwangwoo Kim4, Sang-Cheol Bae6 and So-Young Bang2, 1Hanyang University Institute for Rheumatology Research, Seoul, South Korea, 2Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 3Department of Business Statistics, Hannam University, Daejeon, South Korea, 4Department of Biology, Kyung Hee University, Seoul, South Korea, 5Hanyang University, Guri, South Korea, 6Hanyang University Hospital for Rheumatic Diseases and Hanyang University Institute for Rheumatology Research, Department of Rheumatology, Seoul, South Korea
Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an unpredictable prognosis and increased mortality risk. Although the role of genetics in RA mortality remains undefined, this study aimed to investigate the clinical and genetic contributions to radiographic damage and mortality in female RA patients.
Methods: The Korean patients with RA were recruited from a prospective BAE RA cohort at Hanyang University Hospital for Rheumatic Diseases since 2001. Baseline demographics, clinical features, autoantibodies profiles, and radiologic damage were collected. All patients were genotyped using four-digit HLA–DRB1 typing and genome-wide association study (GWAS). Weighted genetic risk score (wGRS) was calculated from 100 well-validated non-HLA SNPs and HLA–DRB1 haplotypes in amino acid positions 11, 13, 71, and 74. Individual wGRS was tested for associations with clinical features, and radiologic damage by using multivariable regression. Cox proportional hazards models were used to examine the associations with wGRS and mortality.
Results: A total of 1,788 female patients were genotyped and included in the analysis. Mortality data were obtained from registered death records provided by Statistics Korea for the period between 2001 and 2018, with 175 deaths reported during this observation period. Multivariable linear regression analysis was employed to assess the independent effects of genetic risk load on radiographic damage and mortality, irrespective of age and disease duration. The analysis revealed a significant association between ever-smokers and high wGRS with increased radiographic damage. Moreover, patients with erosive RA exhibited a higher incidence risk of all-cause mortality, even after adjusting for age, smoking status, and disease duration.
Conclusion: The findings of this study demonstrate that genetic risk load, which implicates pathogenesis, could serve as a predictor of a poor clinical course in female patients with RA. These results emphasize the importance of considering genetic factors in assessing the prognosis and mortality risk in RA patients.
J. Kim: None; Y. Lee: None; Y. Park: None; A. Kwon: None; Y. Kwon: None; Y. Joo: None; H. Lee: None; K. Kim: None; S. Bae: None; S. Bang: None.
