Upregulated expression of FFAR2 and SOC3 genes is associated with gout.

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.

Mitochondrial and Oxidative Impacts of Short and Long-term Administration of HAART on HIV Patients.

BACKGROUND: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. METHODS: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/µl, and genomic studies were all done using standard operative procedures. RESULTS: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. CONCLUSION: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.