Association of Human Leukocyte Antigen-G Gene Polymorphisms with Rheumatoid Arthritis: Relationship with Disease Activity, Severity and Treatment Response

Abstract

Background: Human leukocyte antigen (HLA-G) plays a role in inflammation and autoimmune disorders. Variations in the HLA-G gene  may have an effect on rheumatoid arthritis (RA). This study examined the impact of the polymorphisms +3142G>C and 14 bp ins/del on  disease susceptibility, activity, severity, and responsiveness to therapy in a cohort of Egyptian RA patients.

Methods: This case-control  study was done on 75 patients with RA and 75 healthy people. The HLA-G rs1063320 (+3142G>C) and rs66554220 14 bp insertion (ins)/ deletion (del) variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and PCR technique, respectively.

Results: Our finding didn't support an association between HLA-G 14 bp ins/del or the HLA-G +3142G>C variants  and RA susceptibility. Subcutaneous nodules and prolonged morning stiffness were substantially related with the G allele of HLA-G  +3142G>C. We used the disease activity score 28 (DAS-28) to look for a correlation between the HLA-G gene variations and disease  activity, but we were unable to find one. Higher levels of C-reactive protein (CRP) and autoantibodies (anti-citrullinated protein antibodies  (ACPA) and ACPA+ rheumatoid factor (RF)) have been linked to the GG genotype and the G allele of HLA-G +3142G>C. Higher  rheumatoid arthritis severity scale (RASS) was found to be related to the HLAG+3142G>C polymorphism and RA severity. The 14 bp ins/del polymorphism and treatment response were found to be significantly correlated. Patients with the del/del genotype and the del allele  had a significantly higher percentage of satisfactory response to therapy.

Conclusion: The 14 bp ins/del and the +3142G>C of HLA-G gene  didn’t appear to be associated with RA susceptibility in this studied group of RA patients. But in terms of autoantibody production,  severity, clinical phenotype, and treatment responsiveness, it may operate as a genetic modulator of disease phenotype. In this regard,  we propose that rather than serving as a risk factor for the onset of RA, these polymorphisms serve as disease modifiers. Treatment  response and polymorphism were discovered. Patients with the del/del genotype and the del allele had a significantly higher percentage  of satisfactory response to therapy.