Polimorfismos y haplotipos en el gen PADI2 y su relación con la diversificación clínica en pacientes con artritis reumatoide del sur de México.

Abstract

Rheumatoid arthritis (RA) is a progressive autoimmune disease characterized by inflammation, pain, and joint limitation. The citrullination is a process mediated by peptidyl arginine deiminase (PADI) enzymes and is recognized as the main trigger for RA`s autoimmunity. The levels of PADI2 have been correlated with elevated clinical activity and anti-CCP levels in RA. Polymorphisms in the PADI2 gene could be associated with the citrullination level, the serological pattern, and RA`s pathological process. This study`s objective was to evaluate the association between the rs2235926, rs2057094 and rs1005753 polymorphisms in the PADI2 gene with RA`s clinical variability in patients from southern Mexico. Methods: A cross-sectional study was carried out. The rs2057094, rs2235926 and rs1005753 polymorphisms of the PADI2 gene were genotyped by TaqMan real-time PCR assay. A rheumatology specialist evaluated the patient`s clinical characteristic and autoantibodies levels (rheumatoid factor, anti-CCP and anti-vimentin) were determined by immunonephelometry and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using STATA version 14 software and haplotype estimation in the SHEsis program. Results: Allele T carriers of rs2235926, rs2057094 and rs1005753 in the PADI2 gene, present higher levels of ACPA and RF, compared to non-carriers. The TT genotype of rs22355926 is related to high levels of RF (p = 0.03). Carriages of the TTT haplotype had an increased risk to present high radiological index (p = 0.001). Conclusion: The polymorphisms and haplotypes in the PADI2 gene are associated to serological characteristics and predictive markers of progression in RA patients from southern Mexico.