Kyoto University · 의학
Satoshi Yoshiji 교수의 연구실은 대사질환, 특히 당뇨병과 관련된 유전적 및 분자 메커니즘을 중심으로 연구를 진행하고 있습니다. 주로 MODY 유형 중 하나인 PDX1-MODY의 유전적 기반과 임상적 표현형의 다양성을 규명하며, 당뇨병의 유전적 기초를 밝혀내는 데 초점을 맞추고 있습니다. 또한 DPP-4 억제제와 관련된 블리스터성 피부질환, 비만이 심혈관 및 대사질환에 미치는 영향을 단백질 수준에서 규명하는 연구를 통해 임상적 약물 타겟을 탐색하고 있습니다. 최근에는 다양한 인종 집단을 대상으로 한 단백질-표현형 연관 분석을 통해 보다 포괄적인 질병 메커니즘을 규명하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Bullous pemphigoid (BP) is an autoimmune blistering skin disorder. Recently, BP induced by dipeptidyl peptidase-4 (DPP-4) inhibitors has been a concern. Although DPP-4 inhibitors are commonly used in the Asian population because of their safety and efficacy, BP associated with DPP-4 inhibitors is sometimes seen in clinical settings. Here, we report five Japanese cases of BP associated with the agents. In the present cases, BP occurred in older adults using four different DPP-4 inhibitors, which
The reduction in HbA1c, but not body weight, is associated with cardiovascular and renal outcomes. The magnitude of HbA1c reduction can be a surrogate for the cardiovascular and renal benefits of treatment with GLP-1 RAs.
We identified the first Japanese family with <i>PDX1</i>-MODY. The similarities and differences found among the cases highlight the wide phenotypic spectrum of <i>PDX1</i>-MODY.
Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen t
Abstract Circulating proteins influence disease risk and are valuable drug targets. To enhance the discovery of protein-phenotype associations and identify potential therapeutic targets across diverse populations, we conducted proteome-phenome-wide Mendelian randomization in three ancestries, followed by comprehensive sensitivity analyses. We tested the potential causal effects of up to 2,265 unique proteins on a curated list of 355 distinct phenotypes, assessing 726,035 protein-phenotype pairs
Previous studies reported associations between obesity measured by body mass index (BMI) and coronavirus disease 2019 (COVID-19). However, BMI is calculated only with height and weight and cannot distinguish between body fat mass and fat-free mass. Thus, it is not clear if one or both of these measures are mediating the relationship between obesity and COVID-19. Here, we used Mendelian randomization (MR) to compare the independent causal relationships of body fat mass and fat-free mass with COVI
Clinicians must be aware of chronic adrenal insufficiency as a possible complication of unilateral adrenalectomy, especially when patients who underwent unilateral adrenalectomy experience severe adrenal stress.
Fasting and meal-induced C-peptide levels are associated with glycemic response to dulaglutide, among which FCPR is least confounded by baseline glycemic control, suggesting its utility as a marker for glycemic response to dulaglutide.
Abstract Obesity is a major risk factor for COVID-19 severity; however, the mechanisms underlying this relationship are not fully understood. Since obesity influences the plasma proteome, we sought to identify circulating proteins mediating the effects of obesity on COVID-19 severity in humans. Here, we screened 4,907 plasma proteins to identify proteins influenced by body mass index (BMI) using Mendelian randomization (MR). This yielded 1,216 proteins, whose effect on COVID-19 severity was asse
Improvement in chronic eGFR slope, which reflects the stabilization of kidney function, is significantly associated with the efficacy of the SGLT2 inhibitor in HF, highlighting the cardiorenal axis role in the beneficial effects on HF. The chronic eGFR slope can be a surrogate marker of the effects of SGLT2 inhibitors on HF reduction.
Abstract Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity has broad effects on circulating protein levels, we investigated circulating proteins that mediate the effects of obesity on coronary artery disease (CAD), stroke, and type 2 diabetes—since doing so may prioritize targets for therapeutic intervention. By integrating proteome-wide Mendelian randomization (MR) screening 4,907 plasm
HbA1c reduction, not bodyweight change, was significantly and proportionally associated with MACE risk reduction. HbA1c lowering may serve as a useful surrogate for the cardiovascular improvements associated with GLP-1RAs in type 2 diabetes.
We established a nationwide genetic testing platform and identified carriers of actionable variants, offering possibilities for precision medicine. Neither classical criteria nor the MODY probability calculator identified all monogenic cases, highlighting the need for broader genetic testing.
Abatacept, a cytotoxic T lymphocyte antigen-4 immunoglobulin recombinant fusion protein, is an immunosuppressive agent indicated for rheumatoid arthritis. Although no significant increase in malignancy has been reported in abatacept-treated patients, whether or not abatacept accelerates tumor progression in specific cancer types remains unclear. We herein report a 66-year-old woman who showed unusually rapid progression of hepatocellular carcinoma following abatacept therapy for rheumatoid arthr