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Single nucleotide polymorphisms (SNP) in the IL-4 receptor, IL-4, and CD40 loci and outcome prediction in patients with early immune-mediated inflammatory polyarthritis

Sauvageau, Gabrielle; Carrier, Nathalie; de Brum-Fernandez, Arthur J.; Liang, Patrick; Masetto, Ariel; Daniel, Claude; Boire, Gilles (2016). Single nucleotide polymorphisms (SNP) in the IL-4 receptor, IL-4, and CD40 loci and outcome prediction in patients with early immune-mediated inflammatory polyarthritis In: EULAR 2016 (Annual European Congres of Rheumatology), June 08-11 2016, London, England.

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Résumé

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Background Clinicians need reliable biomarkers of disease progression contributing additional information sufficient to personalize treatments in patients with early immune-mediated inflammatory polyarthritis (EPA) and rheumatoid arthritis. Some single nucleotide polymorphisms (SNP) in immune-related genes impact the expression of encoded proteins.

Objectives To determine whether SNP in the Interleukin (IL)-4 Receptor (IL-4R), IL-4, and CD40 genes are associated with EPA disease outcomes.

Methods We studied patients from the Early Undifferentiated PolyArthritis (EUPA) cohort. These patients were evaluated early (median 3.8 months), treated to remission and followed up at pre-specified intervals. Radiographs were scored according to Sharp/van der Heijde (SvH); significant damage was ≥5. SNPs were genotyped using an allele-specific primer extension (ASPE) assay and Luminex 100 analyzer. HLA-DR alleles were determined using the LABType rSSO assay (One Lambda). SNP and HLA-DR alleles were correlated to total (SvH ≥5) or erosive (Erosion ≥5) joint damage, functional incapacity (Modified Health Assessment Questionnaire (M-HAQ) ≥1.0) and remission according to Simplified disease activity index (SDAI ≤3.3) using generalized estimating equation (GEE) with repeated measures over 5 years. Results were presented with relative risk (RR) and 95% confidence intervals (CI). General linear model (GLM) with repeated measures was used for continuous outcomes.

Results The allelic distribution for the SNPs is presented in Table. IL-4 SNPs rs2243250 and rs2070874 were strongly correlated (r2=0.99); only rs2243250 is presented. The (G) allele at rs1801275 (IL-4R) was significantly associated with decreased radiographic damage (GLM: Estimate (standard error): 0.035 (0.017), p=0.043). A (T) allele at rs2243250 (IL-4) was positively associated with erosive damage (GEE: RR 1.26 (1.02–1.55), p=0.034) and functional incapacity (M-HAQ ≥1.0; GEE: RR 1.25 (1.00–1.55), p=0.048). A (T) allele at rs4810485 (CD40) was associated with a higher likelihood of reaching SDAI remission (GEE: RR 1.36 (1.13–1.64), p=0.001). As previously published1, the presence of at least one copy of the DERAA protective alleles was significantly associated with decreased erosive damage (GEE: RR 0.75 (0.58–0.96), p=0.02), a trend to decreased functional incapacity (GLM: M-HAQ ≥1.0; RR: 0.79 (0.61–1.02), p=0.07) and increased chance of SDAI remission (GEE: RR 1.19 (1.01–1.4), p=0.04). Combined presence of at least one copy of the DERAA alleles and two copies of rs2243250 (C) allele of IL-4 further reduced erosive damage (GEE: RR 0.67 (0.51–0.90), p=0.007), functional incapacity (GLM: RR 0.75 (0.56–1.00), p=0.051) and slightly increased the chance for SDAI remission (GEE: RR 1.21 (1.02–1.44), p=0.03).

Figure1 (omisse)

Conclusions Genotyping the SNP rs1801275 (IL-4R), rs2243250 (IL-4), rs1883832/rs4810485 (CD40) and determining the HLA-DR allele of EUPA patients provided a set of stable genetic predictors of disease progression, both clinically and on radiographs. Their association together and with other stable predictors may contribute to develop reliable biomarker signatures suggesting significant associations with poor disease outcomes.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Annals of the Rheumatic Diseases 75 (suppl. 2) OP0243
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 12 mars 2019 15:07
Dernière modification: 12 mars 2019 15:07
URI: http://espace.inrs.ca/id/eprint/5858

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