[Pharmacogenomics of the immunosuppressive agents].
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Antirheumatic Agents↗
Biomedical subjects
Atsuo Taniguchi
Publications and source records attributed to Atsuo Taniguchi.
The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis.
OBJECTIVE: To clarify the mechanism of decreased serum uric acid (SUA) concentrations during acute gouty arthritis. METHODS: Data from patients with acute gouty arthritis during and after an attack were investigated retrospectively. Other investigations, including changes in urinary excretion and biochemical markers, were performed prospectively. RESULTS: SUA was significantly lower in the acute phase (7.5 +/- 1.4 mg/dl) than in the intercritical phase (8.5 +/- 0.9 mg/dl) (p < 0.0001). During the acute gout phase, a normal SUA level was found in 20 of 41 patients (49%). C-reactive protein (CRP) during acute attacks was significantly correlated with plasma interleukin 6 (IL-6) and cortisol (r = 0.645, p < 0.005; r = 0.460, p < 0.05). Percentage change in SUA at onset of attack correlated with CRP and IL-6 (r = 0.762, p < 0.0001; r = 0.630, p < 0.005), as well as with increased urinary excretion of uric acid, estimated by percentage change in fractional excretion of uric acid (FEua) during attack (r = 0.447, p < 0.05). Further, change in FEua was correlated with plasma cortisol levels during the acute attack (r = 0.534, p < 0.05). CONCLUSION: Decrease in SUA during acute gouty arthritis is associated with increased urinary excretion of uric acid; an inflammatory process may play a role in the mechanism.
Acute Disease↗
Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene.
OBJECTIVE: N-acetyltransferase 2 (NAT2) is a key enzyme for the acetylation of sulfasalazine (SSZ). We examine whether there was a correlation between diplotype configurations (combinations of 2 haplotypes for a subject) at the NAT2 gene and the adverse effects of SSZ used for the treatment of rheumatoid arthritis (RA). METHODS: The findings from 144 patients with RA who had been treated with SSZ were collected from our outpatient department and used for a retrospective study. Haplotype analysis was performed by the maximum-likelihood estimation based on the EM algorithm using the obtained polymorphism data. RESULTS: Sixteen patients (11.1%) had experienced adverse effects from SSZ, the most common being allergic reactions including rash and fever. The slow acetylators who had no NAT2*4 haplotype had experienced adverse effects more frequently (62.5%) than the fast acetylators who had at least one NAT2*4 haplotype (8.1%) (p < 0.001, OR 7.73, 95% CI 3.54-16.86). In 25% of the slow acetylators, the adverse effects were so severe that they were hospitalized. CONCLUSION: Genotyping the NAT2 gene followed by estimation of diplotype configuration before administration of SSZ is likely to reduce the frequency of adverse effects in Japanese patients with RA.
Acetylation↗
[Pharmacogenetics of disease modifying anti-rheumatic drugs].
There are large differences in the effectiveness of disease modifying anti-rheumatic drugs(DMARD) from one person to the next. Adverse drug reactions caused by DMARD can also occur to some patients, but do not occur to others. One possible cause of the differences in the effectiveness and adverse drug reactions is genetic variation in how individuals metabolize drugs. The Human Genome Project heralds new opportunities for using information about genetic variation to predict responses to drug therapies, called pharmacogenetics. Based on pharmacogenetics, tailor-made drug therapy is going to be realized. Our recent studies revealed the relationship between genetic polymorphisms of drug metabolizing enzymes and the efficacy of methotrexate or sulfasalazine in patients with rheumatoid arthritis, suggesting pharmacogenetics is applicable to the treatment of rheumatoid arthritis.
Antirheumatic Agents↗