Background/Purpose: Genetic contribution of SNP (single nucleotide polymorphism) of TNFα–308 promoter and FoxI for VDR (vitamin D receptor) polymorphism on disease severity and outcome in JIA is not yet well established. VDR polymorphisms correlations with different autoimmune diseases have been implicated and found to be different in some populations but data for JIA are missing. Primary endpoint of this study was to evaluate influence of these promoter polymorphisms, as possible biomarkers, on disease severity and long term outcome in JIA patients on anti-TNF treatment.

Methods: Genomic DNA was extracted and TNFα–308 promoter and FokI VDR polymorphism was evaluated using the PCR-RFLP method in 60 JIA patients included in Serbian JIA registry who donated blood samples before commencement of etanercept treatment. Time cut of point for outcome data analysis was 4 years after first dose of anti-TNF agent (etanercept).

Results: At enrolment JIA patients mean age was 14.7±4.22, disease duration 6.59±2.76, and average dose of MTX 11.91±6.68 mg/m2/week. Disease subtype distribution was 6.78% systemic, 54.24% polyRF- and extended oligo, 18.64% polyRF+, 16.95% ERA and 3.38 PsA. The distribution of TNFα308 and VDR genotypes was not significantly different among JIA subtypes. TNFα308 genotypes distribution was 6.78% AA, 30.51% GG and 62.71% GA. After 4 years  treatment could be stopped (remission) in 35.14%, had to be reintroduces due to disease worsening in 16.22%, disease was in remission under medication in 21.62% or still active in 24.32% GA patients while respectively in 38.9%, 16.7%, 27.8% and 11.1% in GG patients. Average duration of etanercept treatment was 34.61±12.11 months and there was significantly shorter need for treatment duration if GG polymorphism group. VDR genotypes distribution was 51.6% FF, 38.7% Ff and 9.7% ff while in 20 healthy controls only FF (wild type) genotype was present. Presence of ff genotype significantly correlated with worse outcome and disease severity. We have found significant correlations with disease severity and presence of TNFα308 and/or FokI VDR genotypes.

Conclusion: Our results indicate that JIA patients, more frequently than healthy controls, have Ff or ff VDR FokI polymorphism. Heterozygote or homozygote presence of f variant for FokI polymorphism of VDR in JIA patients was associated with more severe disease and worse outcome. JIA patients with GG TNFα308 genotype can achieve better outcome and etanercept treatment can be stopped earlier compared to GA genotype. Both genotypes could be useful clinical predictive biomarker for disease severity and treatment response.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-foki-vdr-and-tnfalpha-308-polymorphism-on-disease-severity-and-long-term-outcome-in-jia-patients-on-anti-tnf-treatment/