Upregulated expression of FFAR2 and SOC3 genes is associated with gout

Abstract

Objective: To examine the expression of Free fatty acid receptor 2 (FFAR2) and Suppressor of cytokine signalling 3 (SOCS3) genes in asymptomatic hyperuricaemia (AH), AH with MSU crystal deposition, inter-critical gout and gout flare.

Methods: Study participants (n = 120) comprised 34 people with serum urate (SU) <360 μmol/l, 69 with AH ± MSU crystal deposition and 17 with a gout flare. Sixteen of the 17 patients with a gout flare attended a second visit 6-12 weeks later. Gene expression levels were assessed using RT-qPCR and results computed as fold changes (FC) after normalization to the reference gene.

Results: FFAR2 was significantly upregulated during gout flares (FC = 2.9) compared with normal SU, AH, and AH + MSU crystal deposition (FC = 1.1, P < 0.0001 for each comparison). FFAR2 was also significantly upregulated during inter-critical gout (FC = 1.8) compared with normal SU, AH and AH + MSU (FC = 1.1, P < 0.001 for each comparison). SOCS3 was significantly upregulated during gout flares (FC = 3.4) compared with normal SU, AH, and AH + MSU crystal deposition (FC = 1.1, 1.1 and 1.2, respectively, P < 0.0001 for each comparison). SOCS3 was also upregulated during inter-critical gout (FC = 2.1) compared with normal SU (P = 0.02) and AH (P = 0.006) (FC = 1.1 and 1.2, respectively). FFAR2 expression was upregulated during gout flare compared with inter-critical gout and SOCS3 expression showed negative correlation with flare duration (r = -0.49, P < 0.05).

Conclusion: FFAR2 upregulation is associated with gout and may trigger gout flares. SOCS3 may have a role in amelioration of gout flares.

Keywords: FFAR2; SOCS3; gene expression; gout.

Graphical abstract

Fig. 1

Expression of FFAR2 and SOCS3 is increased in patients with gout flare and during the inter-critical period Gene expression was carried out using RT-qPCR normalized to RPLP0. Relative expressions are presented as mean fold changes (s.e.m.). (A) FFAR2 expression was increased by 2.9-fold in gout flare patients (n = 17) compared with the non-gout groups—normal serum urate (n = 34), AH (n = 49) and AH+MSU (n = 20) (P < 0.0001). (B) Similarly, SOCS3 expression was increased by 3.4-fold in gout flare when compared with normal serum urate, AH and AH + MSU (P < 0.0001 for each). (C) FFAR2 remained upregulated in inter-critical gout (n = 16) by 1.8-fold compared with normal serum urate (fold change = 1.1, P = 0.004), AH (fold change = 1.1, P = 0.001) and AH + MSU (fold change = 1.1, P = 0.005). (D) SOCS3 expression remained upregulated in inter-critical gout by 2.1-fold compared with normal SU (fold change = 1.1, P = 0.02) and AH (fold change = 1.0, P = 0.01). Fold changes between non-gout groups and gout flare and inter-critical gout groups, respectively, were compared using one-way ANOVA with Bonferroni correction for multiple testing. ****P < 0.0001 was significant with respect to the gout flare group. **P < 0.004 and *P = 0.02 with respect to the inter-critical gout group. FFAR2: Free fatty acid receptor 2; SOCS3: Suppressor of cytokine signalling 3; AH: asymptomatic hyperuricaemia; SU: serum urate.