PTPN22 GENETIC VARIANTS AS PREDICTORS OF DISEASE SEVERITY AND JOINT DESTRUCTION IN RHEUMATOID ARTHRITIS: EVIDENCE FROM THE UZBEK POPULATION

Rakhimova Madina Bokhodirovna; Akhmedov Khalmurad Sadullaevich

Authors

Rakhimova Madina Bokhodirovna Author
Akhmedov Khalmurad Sadullaevich Author

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive inflammation and joint destruction. The aim of the study was to determine the relationship between the PTPN22 (rs2476601) gene polymorphism and the clinical and immunological manifestations and disease activity in RA patients of the Uzbek population. 120 patients with RA and 60 healthy individuals in the control group were examined. Disease activity was assessed using the DAS28-ESR, CDAI, and SDAI indices, levels of CRP, ACPA, and AMCV were measured, and radiological changes were evaluated using the Sharp scale. Carriers of the minor T-allele demonstrated significantly higher disease activity, autoantibody concentrations, and joint destruction severity compared to those with the CC genotype. An association between the T-allele and high-positive autoantibody status was established (OR = 2.56; p < 0.05). The obtained data suggest a possible role of the PTPN22 polymorphism as a genetic predictor of aggressive RA course in patients of the Uzbek population.

References

1. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an ACR/EULAR collaborative initiative. Arthritis Rheum. 2010;62 (9):2569-2581.

2. Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2020;79 (6):685-699.

3. Prevoo MLL, van 't Hof MA, Kuper HH, et al. Modified disease activity scores that include twenty-eight-joint counts (DAS28). Arthritis Rheum. 1995;38 (1):44-48.

4. Smolen JS, Breedveld FC, Schiff MH, et al. A simplified disease activity index (SDAI) and a clinical disease activity index (CDAI) for RA. Arthritis Rheum. 2003;48 (9):2437-2441.

5. van der Heijde DMFM. Plain X-rays in rheumatoid arthritis: overview of scoring methods and their application (Sharp/van der Heijde). J Rheumatol. 2000;27 (1):261-263.

6. van der Heijde DMFM, van Leeuwen MA, van Riel PLCM, et al. Biannual radiographic assessments of hands and feet in RA: reliability of a modification of the Sharp score. Arthritis Rheum. 1992;35 (1):26-34.

7. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111 (12):1805-1812.

8. Brigden ML. The erythrocyte sedimentation rate: still a helpful test when used wisely. Am Fam Physician. 1999;60 (5):1443-1450.

9. Schellekens GA, de Jong BAW, van den Hoogen FHJ, et al. Citrulline is essential for the antigenicity of RA-specific anti-filaggrin autoantibodies. J Clin Invest. 1998;101 (1):273-281.

10. Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-CCP and rheumatoid factor for RA. Ann Intern Med. 2007;146 (11):797-808.

11. Nicaise-Roland P, Nogueira L, Demattei C, et al. Autoantibodies to mutated citrullinated vimentin (anti-MCV) in early RA: diagnostic and prognostic value. Ann Rheum Dis. 2009;68 (9):137-141.

12. Begovich AB, Carlton VEH, Honigberg LA, et al. A missense single-nucleotide polymorphism in PTPN22 is associated with RA. Am J Hum Genet. 2004;75 (2):330-337.

13. Plenge RM, Padyukov L, Remmers EF, et al. Replication of PTPN22 association and its contribution to RA susceptibility. Am J Hum Genet. 2005;77 (6):1044-1050.

14. Okada Y, Wu D, Trynka G, et al. Genetics of RA contributes to biology and drug discovery. Nature. 2014;506 (7488):376-381.

15. Endothelin-1biomarker Features In Patients With Ankylosing Spondylitis After COVID-19. M Rakhimova, K Akhmedov, M Tagaeva, S Sadikova - Journal of positive school psychology, 2022