Genetic association of the functional CDHR3 genotype with early-onset adult asthma in Japanese populations

BackgroundRecent studies have demonstrated that a coding SNP (rs6967330, Cys529→Tyr) in cadherin-related family member 3 (CDHR3), which was previously associated with wheezing illness and hospitalizations in infancy, could support efficient human rhinovirus C (RV-C) entry and replication. Here, we sought to examine the genetic contribution of this variant to the development of adult asthma.MethodsWe performed a candidate gene case–control association study of 2 independent Japanese populations (a total of 3366 adults). The odds ratios (ORs) for association of the A allele at rs6967330 with adult asthma were calculated according to age at onset of asthma. In addition, the effect of the CDHR3 genotype on the development of specific asthma phenotypes was examined.ResultsThe A allele was associated with asthma (OR = 1.56; Mantel–Haenszel p = 0.0040) when the analysis was limited to patients with early-onset adult asthma. In addition, when the analysis was limited to atopic individuals, a stronger association of the CDHR3 variant with early-onset asthma was found, and interaction of the CDHR3 genotype with atopy was demonstrated. Finally, a significant association of this variant was specifically found with a phenotype of asthma characterized by atopy, early-onset, and lower lung function.ConclusionsOur study supports the concept that the CDHR3 variant is an important susceptibility factor for severe adult asthma in individuals who develop the disease in early life. The interaction between the CDHR3 variant and atopy indicates that genetic predisposition to early respiratory viral infection is combined with atopy in promoting asthma

Association analyses of eQTLs of the TYRO3 gene and allergic diseases in Japanese populations

BackgroundTYRO3 is a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family and functions to limit type 2 immune responses implicated in allergic sensitization. Recent studies have shown that multiple intronic variants of TYRO3 were associated with asthma, implying that genetic variation could contribute to errant immune activation. We therefore hypothesized that expression quantitative trait loci (eQTLs) of the TYRO3 gene influence the development of allergic diseases (including asthma and allergic rhinitis) in Japanese populations.MethodsWe performed a candidate gene case–control association study of 8 eQTLs of TYRO3 on atopy, asthma, and allergic rhinitis using 1168 unrelated Japanese adults who had GWAS genotyping. We then examined the genetic impact of rs2297377 (TYRO3) on atopy and allergic rhinitis in 2 other independent Japanese populations.ResultsA meta-analysis of 3 Japanese populations (a total of 2403 Japanese adults) revealed that rs2297377 was associated with atopy and allergic rhinitis (OR = 1.29 and 1.31; P = 0.00041 and 0.0010, respectively). The risk allele at rs2297377 correlated with decreased expression of TYRO3 mRNA. The gene–gene interaction between HLA-DPB1 and TYRO3 was not significant with regard to sensitization. The estimated proportion of atopy and allergic rhinitis cases attributable to the risk genotype was 14% and 16%, respectively.ConclusionsOur study identified TYRO3 as an important susceptibility gene to atopy and allergic rhinitis in Japanese

Cost of illness of hepatocellular carcinoma in Japan: A time trend and future projections.

BACKGROUND:Hepatocellular carcinoma (HCC) is the fifth leading cause of death in Japan. The aim of this study was to calculate the social burden of HCC using the cost of illness (COI) method, and to identify the key factors driving changes in the economic burden of HCC. METHODS:Utilizing government-based statistical nationwide data, the cost of illness (COI) method was used to estimate the COI for 1996, 1999, 2002, 2005, 2008, and 2014 to make predictions for 2017, 2020, 2023, 2026, and 2029. The COI comprised direct and indirect costs (morbidity and mortality costs) of HCC. RESULTS:From 1996 to 2014, COI trended downward. In 2014, COI (579.2 billion JPY) was 0.71 times greater than that in 1996 (816.2 billion JPY). Mortality costs accounted for more than 70% of total COI and were a major contributing factor to the decrease in COI. It was predicted that COI would continue a downward trend until 2029, and that the rate of decline would be similar. CONCLUSIONS:COI of HCC has been decreasing since 1996. Treatment of patients infected with hepatitis C virus using newly introduced technologies has high therapeutic effectiveness, and will affect the future prevalence of HCC. These policies and technologies may accelerate the downward tendency of COI, and the relative economic burden of HCC is likely to continue to decrease

Cost of illness of ischemic heart disease in Japan: a time trend and future projections

Abstract Background Ischemic heart disease (IHD/ICD10: I20-I25) is the second leading cause of deaths in Japan and accounts for 40% of deaths due to heart diseases. This study aimed to calculate the economic burden of IHD using the cost of illness (COI) method and to identify key factors that drive the change of the economic burden of IHD. Methods We calculated the cost of illness (COI) every 3 years from 1996 to 2014 using governmental statistics. We then predicted the COI for every 3 years starting from 2017 up to 2029 using the fixed and variable model estimations. Only the estimated future population was used as a variable in the fixed model estimation. By contrast, variable model estimation considered the time trend of health-related indicators over the past 18 years. We derived the COI from the sum of direct and indirect costs (morbidity and mortality). Results The past estimation of COI slightly increased from 1493.8 billion yen in 1996 to 1708.3 billion yen in 2014. Future forecasts indicated that it would decrease from 1619.0 billion yen in 2017 to 1220.5 billion yen in 2029. Conclusion The past estimation showed that the COI of IHD increased; in the mixed model, the COI was predicted to decrease with the continuing trend of health-related indicators. The COI of IHD in the future projection showed that, although the average age of death increased by social aging, the influence of the number of deaths and mortality cost decreased

Indium(III)-Catalyzed Knoevenagel Condensation of Aldehydes and Activated Methylenes Using Acetic Anhydride as a Promoter

The combination of a catalytic amount of InCl₃ and acetic anhydride remarkably promotes the Knoevenagel condensation of a variety of aldehydes and activated methylene compounds. This catalytic system accommodates aromatic aldehydes containing a variety of electron-donating and -withdrawing groups, heteroaromatic aldehydes, conjugate aldehydes, and aliphatic aldehydes. Central to successfully driving the condensation series is the formation of a geminal diacetate intermediate, which was generated in situ from an aldehyde and an acid anhydride with the assistance of an indium catalyst

Quality assessment of clinical practice guidelines using the AGREE instrument in Japan: A time trend analysis.

BackgroundClinical practice guidelines (CPGs) are representative methods for promoting the standardization of healthcare and improvement of its quality. Few studies have investigated changes in the quality of CPGs published in a country over time. Our aim was to investigate changes in the quality of CPGs over time in the context of the available infrastructure for CPG development, public interest in healthcare quality, and healthcare providers' responses to this interest.MethodsAll CPGs pertaining to evidence-based medicine (EBM) issued between 2000 and 2014 in Japan (n = 373) were evaluated using the Japanese version of the Appraisal of Guidelines for Research and Evaluation (AGREE) I. Additionally, time trends in quality were analyzed. Using a cut-off point based on the publication year of CPG development literature, the evaluated CPGs were classified into those published until 2008 (pre-2008) and those published since 2009 (post-2008). Subsequently, we compared these groups in terms of 1) first edition CPGs and its second editions, and 2) patients' version of CPGs.ResultsScores on all six domains of AGREE I improved each year. A comparison of the first- and second-edition of CPGs (n = 64) showed that scores on all domains improved significantly after revision. Significant improvement was observed in three domains (#2 stakeholder involvement, #3 rigor of development, and #4 clarity of presentation) in the pre-2008 group and in all domains in the post-2008 group. The comparison between the pre- and post-2008 groups in terms of CPGs for patients showed that the score increased in only one domain (#1 scope and purpose).ConclusionsThe number of published CPGs has been increasing and the quality of CPGs, as assessed using the AGREE I instrument, has been improving. These changes seem to be influenced by improvements in social infrastructure, such as the publication of CPG development procedures, availability of CPG preparation methodology training, and increase in CPG-related skills