Primary biliary cirrhosis (PBC) is a multifactorial disease in which genetic factors rather than environmental factors may predominantly contribute to the pathogenesis. In order to identify the genetic determinants of the disease severity and progression of PBC, we examined an association of seven tag single-nucleotide polymorphisms (SNPs) in the multidrug resistance protein 3 (MDR3/ABCB4) gene in 148 Japanese PBC patients and 150 age-and sex-matched healthy control subjects. SNPs were detected via polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR direct DNA sequencing methods. Subsequently, haplotypes were constructed from three tag SNPs (rs31658, rs31672, and rs1149222) that were significantly associated with progression of PBC. Logistic regression analyses revealed that a Hap 2 haplotype and its homozygous diplotype, Hap 2/Hap 2, in MDR3 were closely associated with the susceptibility to jaundice-type progression of PBC [P ‫؍‬ 0.004, odds ratio (

Major adverse cardiovascular events (MACEs), such as stroke and myocardial infarction (MI), are the most common cause of death worldwide (the second leading cause in Japan), and their prevention is critical in healthcare. 1-3 Hypertension, hyperlipidemia, and diabetes mellitus are known risk factors for MACEs, and a number of pharmaceutical agents have been developed to control the risk

These results suggested that the genetic variants of CYP7A1 and its transcriptional activators (HNF4A and PPARGC1A) may activate bile acid synthesis, resulting in the accumulation of bile acids in hepatocytes and eventually leading to the predisposition to PBC progression. Thus, the regulation of CYP7A1 expression may represent an attractive therapeutic target for cholestatic liver diseases including PBC.

Objectives: This study aims to evaluate the prevalence of hyperuricemia (HU) considering both serum uric acid (SUA) levels and medication status of urate-lowering drugs (ULDs), and the association between HU and its comorbidities using a Japanese healthcare database. Materials and Methods: The study population consisted of 60,828 subjects who had at least one serum uric acid measurement between the fiscal years (FYs) 2010 and 2014 in a Japanese employment-based health insurance database (MinaCare Co., Ltd., Tokyo, Japan), which includes mutually linked medical/pharmaceutical claims data and health checkup data. Hyperuricemia was defined as a SUA level >7.0 mg/dL of the health checkup data and/or a prescription for a ULD. The association between HU and comorbidities were analyzed by comparing the prevalence of HU of each subgroup defined by presence or absence of comorbidity. Results: The prevalence of HU in FY 2014 was 26.8% (95% confidence interval [CI]: 26.2 to 27.3%) in male subjects and 0.9% (95% CI: 0.7 to 1.0%) in female subjects. According to the analyses by sex and age, a trend of increasing prevalence with age was observed in both males and females. The prevalence of HU remained stable both in males and females from FYs 2010 to 2014. The positive association between HU and well-known comorbidities were confirmed with the exception of diabetes mellitus and smoking status in male subjects. Conclusion: Our results provided a more accurate prevalence of HU in Japanese population. It is important to increase the awareness on HU in the society to reduce the burden of HU-related diseases.

Xanthine oxidoreductase (XOR) inhibitors, such as allopurinol and febuxostat, inhibit the catalysis of serum uric acid (SUA) synthesis. In doing so, they are thought to improve vascular endothelial function in patients with hyperuricemia and cardiovascular risk by reducing increases in SUA and reactive oxygen species levels. We performed a retrospective cohort study to evaluate the effects of topiroxostat, a novel XOR inhibitor, on vascular function measured by flow‐mediated dilation (FMD) on ultrasonography. In total, 23 patients with hyperuricemia were enrolled. After approximately 8 weeks, topiroxostat was associated with a significant increase in the peak percentage change in diameter (∆FMD) from 4.53% ± 2.09% to 5.54% ± 3.08% (P = .045). It also significantly reduced the SUA levels from 7.31 ± 1.43 to 5.44 ± 1.11 mg/dL (P < .001). Although further studies are needed to validate these results, it appears that topiroxostat improves vascular endothelial function in patients with hyperuricemia.