Association of HLA-E*01:01/*01:03 polymorphism with methotrexate-based treatment response in South Indian rheumatoid arthritis patients

Abstract

ObjectivesNon-classical HLA-E molecules may influence the disease susceptibility and phenotype including treatment response in chronic inflammatory disorders such as Rheumatoid Arthritis (RA) by virtue of their capacity to modulate innate immune processes. This study was carried out to investigate the role of HLA-E polymorphism in RA susceptibility, clinical and serological phenotype as well as treatment response. MethodsGenomic DNA from 221 RA patients and 200 healthy controls (HC) were typed for HLA-E rs2844724 (C/T) and rs1264457 (HLA-E*01:01/*01:03) single nucleotide polymorphisms (SNPs) using the TaqMan 5'nuclease assay consisting of allele-specific fluorogenic oligonucleotide probes. ResultsOur study did not find any association between HLA-E polymorphism and RA susceptibility or disease phenotype. However, it was observed that the frequency of HLA-E*01:03 allele was higher in all RA cases (Pc = 0.03, OR = 3.02, 95% CI = 1.06–9.39), young onset RA (YORA) (Pc = 0.03, OR = 3.20, 95% CI = 1.11–9.98) and female RA (Pc = 0.04, OR = 3.04, 95% CI = 1.06–9.46) patients who responded well (good responders) to a combination of non-biological disease modifying anti rheumatic drugs (DMARDs), methotrexate (MTX) and hydroxychloroquine (HCQ) as compared to non-responders. Moreover, the frequency of rs2844724 T allele and TT genotype was observed to be higher in patients with low titers of rheumatoid factor (RF) than those with high titers (90% vs. 77% and 79% vs. 59% respectively), although the difference did not reach statistical significance. ConclusionThe results of our study suggest that HLA-E rs1264457 may influence the patient response to treatment with methotrexate-based DMARD therapy. Thus, it may be a useful genetic marker for treatment response in patients with RA.