Role of HLA-DRB1, PTPN22, CTLA4 Gene Polymorphisms in Susceptibility to Rheumatoid Arthritis

Abstract

Background and AIM: The genetic and environmental factors are believed to play an important role in the pathogenesis of rheumatoid arthritis (RA), the precise etiology is still uncertain. Regarding its genetic components, the strongest genetic association with RA is that found for certain alleles of HLA-DRB1. Recent studies have revealed that the single‐nucleotide polymorphism (SNP) of non-HLA PTPN22 and CTLA4 gene were associated with RA. The associations of HLA, PTPN22 and CTLA4 polymorphisms with RA risk have been less well replicated. Thus, the current study was undertaken to investigate the effects of HLA-DRB1, PTPN22, CTLA4 gene polymorphisms and autoantibodies in susceptibility to RA. Methods: A total of 200 patients fulfilled the criteria for RA and 200 healthy individuals were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) were measured by enzyme-linked immunosorbent assay (ELISA). HLA-DRB1 alleles were determined by polymerase chain reaction-sequence specific primer (PCR-SSP) method. Samples were genotyped for PTPN22 1858C/T (rs2476601) and CTLA4 CT60 (rs3087243) variants using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: In RA patients 88% and 82% were positive for anti-CCP and RF autoantibodies, respectively. A significant increase in the frequency of HLA-DRB1*01, HLA-DRB1*04, HLA-DRB1*10, HLA-DRB1*14 shared epitope (SE) alleles were identified in RA patients, whereas in healthy subjects, they were HLADRB1*03, HLA-DRB1*07, HLA-DRB1*11, HLA-DRB1*13. There was no association of the PTPN22 1858T variant with RA and it seems to be independent of MHC associations. The frequency of CTLA4 CT60 A allele carriers was significantly higher in RA patients and also it is preferentially in SE-positive RA patients. Conclusion: Our results confirmed the previously reported HLA-DRB1 SE alleles associations with RA. The CTLA4 polymorphism appears to interfere with HLA-DRB1 susceptibility to RA. On the other hand, we failed to provide evidence for the association of the PTPN22 SNP with RA.