Gout is a common arthritis caused by monosodium urate crystals. Familial studies have shown that the heritability of serum urate levels is estimated to be 30-70%. By a gene-based test, a recent study suggested that rare variants are major contributors to the heritability of serum urate levels. Gene-based analysis considers the effect of multiple genetic variants in one gene in a single test. In this article, the relationship between the sample size and potency of a gene-based test was examined. We divided a hypothetical population into two groups: those who have rare variations and those who do not. It was considered that the difference in uric acid concentrations between the two groups was the same as the difference caused by the presence or absence of URAT1 variants in previous studies. Uric acid levels in each person were also considered to follow a normal distribution, with the expectation being the average of the group to which the person belonged. Under these conditions, the statistical power of the gene-based test was computed. The results showed that the gene-based test boosted the power of the test so that rare variants were detected in far fewer people than the SNP-based test. This study suggests the potential for studying "common diseases, rare variations" by a gene-based test, in addition to "common diseases, common variations.”
Background and Objectives: Melinjo is a tree native to Indonesia. Melinjo seed extract (MSE) contains gnetin C, gnetin L, and gnemonosides as resveratrol dimer derivatives. The seeds are particularly rich in gnetin C. In human clinical trials, relatively high-dose intake of MSE reportedly decreased serum uric acid. We examined the safety and effects of long-term regular-dose MSE intake to decrease serum uric acid, and the relationship with serum concentrations of MSE derivatives.
Methods and Study Design: Subjects with serum uric acid concentrations of 6.0-6.9 mg/dL were divided into 4 groups receiving placebo or MSE at 100, 200, or 300 mg/day for 12 weeks. Subjects with uric acid concentrations of 7.0-7.9 mg/dL took 300 mg of MSE. Serum MSE derivatives at 12 weeks were measured in subjects who took MSE at 300 mg/day.
Results: Ninety-eight men participated and 11 of those participants dropped out of this trial.No significant adverse events were detected, whereas no significant serum uric acid changes were detected. Serum concentrations of gnetin C monoglucuronide and total gnetin C (gnetin C+gnetin C monoglucuronide), representing major derivatives of MSE, tended to correlate with decreased serum uric acid concentrations. The subjects with total gnetin C ≥ 200 ng/mL showed a decrease in the serum uric acid concentration compared with those with total gnetin C < 200 ng/mL in the group with uric acid ≥ 7.0 mg/dL at week 0.
Conclusions: Regular-dose MSE can be safely ingested, and high serum gnetin C concentrations might decrease serum uric acid.
Hyperuricemia and lifestyle-related diseases are often comorbid in the same subjects.
Therefore, nutrition education is usually included in the educational program for improvement of their life-style. In this study, we investigated retrospectively the effect of nutrition education for the patients of dyslipidemia on their serum uric acid level.
Forty-three subjects of dyslipidemia were enrolled. We investigated the data of body weight, serum lipid profiles, serum uric acid level and so on for 1 year after the first education exposure. The average times of nutrition education was 2.5. In the analysis of the all subjects, body weight significantly decreased in 3 and 12 months after the first education compared to before. Serum LDL cholesterol level significantly decreased from 150.9±32.6mg/dl (before education) to 139.0±35.7mg/dl (3 months) and 132.1±31.9mg/dl (12months). Serum uric acid level did not decrease by education in all subjects. In the analysis of non-medicated hyperuricemia subjects, serum uric acid level decreased significantly after the education. In the group of body weight loss tends to decrease serum uric acid level compared with the group of body weight increase.
In this study, nutrition education for dyslipidemia subjects may be useful for the improvements of the serum uric acid level. The body weight loss might be a good surrogate goal in the education for the improvement of the life style for the decrease of the serum uric acid level.
Fenofibrate (FEN) is not only a lipid-lowering drug, but also has a uric acid-lowering effect, so it is often used for patients with gout and hyperuricemia complicated with metabolic syndrome. We often observe the effect of fibrates to increase the serum creatinine concentration; however, the actual situation, such as the frequency and degree, is unclear. We investigated the renal dysfunction due to FEN administration in patients receiving FEN in our clinic.
From December 2011 when FEN tablets (Tricor tablets, Lipidil tablets) were launched in Japan, to August 2020, we examined the renal function (serum creatinine: SCR, estimated glomerular filtration rate: eGFR) before and after FEN administration in 159 patients who received FEN in our clinic. The SCR significantly increased from 0.83 ± 0.15 mg / dL before administration to 0.97 ± 0.20 mg / dL 1-3 months after administration, and 0.99 ± 0.18 mg / dL 6 months after administration. The eGFR significantly decreased from 81.2 ± 18.8 mL / min / 1.73 m2 before administration to 69.2 ± 14.7 mL / min / 1.73 m21-3 months after administration and 66.7 ± 14.5 mL /min 6 months after administration. Increased SCR and decreased eGFR due to FEN administration were observed in 90% or more of the treated patients, and an increase in SCR of 1.0 mg / dL or more and a decrease in eGFR of 10 mL / min / 1.73 m2 or more were observed in about 70% of the patients. After 6 months, the renal function remained at the same level.
The renal function was examined in 21 patients who discontinued the administration of FEN, but continued to visit our clinic. The SCR decreased from 1.16 ± 0.29 mg / dL to 0.96 ± 0.22 mg / dL and the eGFR increased from 59.7 ± 19.6 mL / min / 1.73 m2 to 71.0 ± 19.8 mL / min2 2-4 months after discontinuation. Regardless of the length of drug administration, SCR and eGFR returned to the pre-dose level, respectively. Although the mechanism of renal dysfunction due to FEN has not been clarified, previous studies indicated the possibility that FEN could cause a reversible reduction in renal blood flow due to the suppression of prostaglandin production.
Renal dysfunction due to FEN was found to be markedly more frequent than the SCR elevation (0.99-3.03%) reported in post-marketing surveillance in Japan. However, FEN is effective in improving dyslipidemia and hyperuricemia; in addition, it is a drug that has been shown to exhibir broad clinical usefulness, such as the improvement of diabetic nephropathy and retinopathy, improvement of the vascular endothelial function, and suppression of cardiovascular events. Considering the balance between benefits and harm, it was considered important to perform regular renal function tests during the administration of FEN.
The validity of using the uric acid excretion fraction by spot urine (FEua spot) has not yet been clarified. Using the deta of "Reference interval of urinary clearance and excretion of urate in Japan (RICE-U)" study and the previously reported cut-off value of FEua spot, 60-minute uric acid clearance (Cua 60 min) or 24-hour uric acid clearance (Cua 24 hr), we examined the degree of agreement of diagnosis by these three types of indicators, the accuracy of each indicator, and the correlation between the indicators. The subjects were indoor workers aged 20 to 65 who participated in the RICE-U study and were not excluded due to lifestyle-related habits or illness. The homology in the diagnosis of underexcretion-type hyperuricemia between each index was evaluated using the kappa coefficient. Also, the coefficient of variation was calculated to compare each test's accuracy, and the correlation between each test was examined. The analysis subjects were 796 people, including 446 males and 350 females. Of the total, 75 people (9.4%) showed hyperuricemia, all of which were males. The concordance rate and κ coefficient for the diagnosis of underexcretion-type hyperuricemia were 71.0% and 0.43 for FEua spot and Cua 24 hr, 72.4% and, 0.42 for FEua spot and Cua 60 min, and 76.0% and 0.48 for Cua 24 hr and Cua 60 min, respectively. The compatibility was all moderate. The coefficient of variation of the three indicators by gender was about the same as 30 to 35%, and a significant positive correlation was observed between the indicators. Three types of renal uric acid excretion index could be substituted for each other. Furthermore, from the viewpoint of versatility, the validity of popularizing the FEua spot, which is excellent convenience, was inferred.