Yoshiki Tsuboi

BACKGROUND: Although utility of composite trait-specific polygenic risk score (multi-trait PRS) has been examined among European ancestries, few studies investigated among East Asians and incorporated modifiable risk factors. We examined the associations of multi-trait PRS for cardiometabolic factors with cardiovascular disease mortality by integrating nongenetic determinants. METHODS: A total of 14 086 Japanese participants (mean age, 55±9; 55.8% women) of the J-MICC (Japan Multi-Institutional Collaborative Cohort) study were analyzed in this study. We calculated 6 PRSs for cardiometabolic traits (systolic blood pressure, body mass index, triglycerides, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and hemoglobin A1c). Based on these PRSs, we developed multi-trait PRS and considered as a primary exposure. Three nongenetic factors (smoking, alcohol drinking, and educational attainment) from the self-reported questionnaire were also examined. RESULTS: During a median 12.1-year follow-up period, a total of 472 all-cause and 79 cardiovascular disease mortality cases were documented. Compared with 0% to 90% of multi-trait PRSs, an adjusted hazard ratio (HR) among the top 10% of multi-trait PRSs was 1.32 (95% CI, 1.00-1.73) for all-cause death and 2.63 (95% CI, 1.48-4.67) for cardiovascular disease death. Incorporation of educational attainment with multi-trait PRSs showed null associations in those who went beyond high school (HR, 2.07 [95% CI, 0.44-9.66]) even in the top 10% of multi-trait PRS. CONCLUSIONS: Our analysis combining both genetic and nongenetic determinants highlighted that lifestyle factors and educational attainment can slightly reduce an individual's composite genetic risk for cardiovascular disease death.

Hand osteoarthritis (HOA), characterized by an earlier onset age and reduced susceptibility to mechanical stress compared with knee and hip osteoarthritis, is considered a suitable disease for identifying predictive biomarkers of osteoarthritis. In particular, DNA methylation variants, expected to contribute to HOA susceptibility, hold potential as osteoarthritis biomarkers. In this study, leukocyte DNA methylation patterns were analyzed in blood samples from patients with HOA, aiming to identify disease-specific biomarkers for osteoarthritis. Using DNA methylation microarrays, we analyzed samples from three subjects with HOA and three age- and gender-matched healthy individuals. For validation, pyrosequencing analysis was conducted using samples from 16 to 9 subjects with and without HOA, respectively. From 735,026 probes in the DNA methylation array, the Top 100 CpG sites associated with HOA, based on low adjusted P-values, including those targeting bone morphogenetic protein 7 (BMP7), SBF2-AS1, PLOD2, ICOS, and CSF1R were identified. Validation analysis revealed significantly higher methylation levels in the BMP7-related site in the HOA group compared with the control group, even after adjusting for age, gender, and body mass index (p = 0.037). In contrast, no significant difference was observed in the other selected CpG sites between the HOA and control groups. This study highlights the significantly increased frequency of methylation at the specific BMP7 site in leukocytes of patients with HOA, suggesting its potential as a biomarker for HOA. Measurement of methylation levels at the CpG sites identified in this study offers a potential approach to prevent future osteoarthritis progression, providing valuable insights into disease management.

BACKGROUND: Among the more than 300 mycotoxins that are known to have toxic effects on animals and humans, Fusarium toxins deoxynivalenol (DON), T-2 and HT-2 toxins (T2/HT2), and zearalenone (ZEN) are frequently detected in domestic agricultural products. This study aimed to assess DON, T2/HT2, and ZEN exposure in Japanese adults by measuring urinary mycotoxins, observing their distributions, and making comparisons with data from other countries. METHODS: A total of 201 individuals participated in the study. Twenty-four-hour urine samples were collected from young adults (34 men and 35 women) in the Tokai region (urban area) and spot urine samples were collected from middle-aged and elderly adults (64 men and 68 women) in the Donan area of Hokkaido Prefecture (rural area). Urinary DON, T2/HT2, and ZEN levels were measured using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: For DON, T2/HT2, and ZEN, the detection frequencies above the limit of detection (LOD) level (0.15, 0.13, and 0.01 µg/L, respectively) in all the samples were 53%, 26%, and 71%, respectively. The median concentrations (95th percentile) of urinary DON, HT2, and ZEN were 0.19 (3.93), <LOD (0.55), and 0.02 (0.12) µg/L, respectively. Although at least one of the investigated mycotoxins was detected in the urine of 86% of study participants, the concentrations were similar to or lower than those found in other countries (from 19 reports within the past decade). Moreover, the probable daily intake (PDI) values in the present study were lower than the provisional maximum tolerable daily intake levels. The urinary mycotoxin levels did not significantly differ with respect to sex, age, or occupation. CONCLUSIONS: This study represents the first comprehensive exposure assessment for DON, T2/HT2, and ZEN in Japanese adults using human biomonitoring methods. These data provide valuable information for a better understanding of mycotoxin exposure in Japan.