観音 隆幸

PURPOSE: This study investigated the association of polygenic risk scores (PRS) and lifestyle factors with type 2 diabetes mellitus development in Japanese populations and evaluated whether PRS can improve diabetes risk prediction beyond traditional risk factors. METHODS: We conducted a cross-sectional and a longitudinal study using the Shika resident cohort (n = 895) and the Toshiba worker cohort (n = 7,019), respectively. Participants were categorized into low, intermediate, and high genetic risk groups using PRS constructed with genome-wide association study data from East Asian populations. We defined diabetes based on hemoglobin A1c, fasting blood glucose, self-reported diagnosis, or medication use. The associations of PRS and lifestyle factors with diabetes development were analyzed using multivariate logistic regression and Cox proportional hazards models. RESULTS: Higher PRS were associated with increased diabetes risk in both cohorts (resident cohort: odds ratio 4.51, 95% confidence interval [CI] 2.53-8.04; worker cohort: hazard ratio 1.82, 95% CI 1.48-2.24 for high vs. low PRS), which remained consistent across age, body mass index, and comorbidities. Regular exercise, absence of hypertension, and absence of dyslipidemia were associated with lower diabetes risk, particularly in the high PRS group. The addition of PRS to conventional prediction models improved the discrimination of diabetes risk. MAIN CONCLUSIONS: PRS are associated with diabetes risk in Japanese general populations, independent of traditional risk factors. Nonetheless, healthy lifestyle habits may reduce diabetes risk even among genetically susceptible individuals, which support the utility of PRS for personalized diabetes risk assessment and prevention strategies.

BACKGROUND: Oxytocin (OXT) signaling through the oxytocin receptor (OXTR) produces stress-relieving effects and modulates alcohol reward and sucrose preference in animal models. These findings suggest the therapeutic potential of OXT for alcohol use disorder (AUD) and liver steatosis. However, human genetic evidence linking OXT signaling to these cravings remains scarce. OBJECTIVE: This study examined the association between the OXTR rs53576 polymorphism and habitual intake of alcohol and sucrose in a general population, with a further focus on related liver pathology. METHODS: A cross-sectional analysis was conducted using data from the Shika study, comprising 696 participants with complete information on both single-nucleotide polymorphisms (SNPs) and dietary intake, assessed using the Brief Dietary History Questionnaire (BDHQ). We examined the association of the rs53576 SNP with alcohol and sucrose consumption, as well as with clinical outcomes related to these dietary factors, including liver enzyme levels and liver steatosis. RESULTS: Among individuals with regular alcohol consumption, those with the rs53576 G/G genotype (under a recessive model) exhibited significantly lower alcohol intake (p = 0.002) and higher sucrose intake (p = 0.004) compared to A allele carriers. An association between rs53576 and aspartate aminotransferase (AST) levels, an indicator of alcoholic liver disease (ALD), further supported the relationship between this genotype and alcohol intake. Sex-stratified analysis revealed that the G/G genotype was linked to a greater prevalence of liver steatosis in women, but not in men. Mediation analysis indicated that this association in women was driven by a direct effect independent of sucrose intake volume. CONCLUSIONS: These findings indicate that the OXTR rs53576 polymorphism is associated with distinct alcohol and sucrose intake patterns and susceptibility to liver steatosis, supporting the potential for genotype-informed nutritional interventions aimed at reducing the risk of AUD, ALD, and metabolic dysfunction-associated steatotic liver disease (MASLD). CLINICAL TRIALS REGISTRATION NUMBER AND WEBSITE WHERE IT WAS OBTAINED: This study was approved by the Ethics Committee for Human Studies at Kanazawa University Hospital (1491, 2016-376) and performed following the principles outlined in the Declaration of Helsinki. Network Clinical Trials Registry (UMIN-CTR) under the registration number UMIN000024915. The detailed trial information is available at the following URL: https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_his_list.cgi?recptno=R000028662.

Although recent studies have reported the association between toxins produced by certain gut microbiota and elevated blood pressure, the relationship between oral frailty (OF) and gut microbiota has rarely been investigated. The purpose of this study was to epidemiologically investigate the relationship between the combination of OF and specific gut microbiota on hypertension in the residents of Shika Town, Ishikawa Prefecture, Japan. A total of 322 residents aged ⩾ 50 years in Shika Town agreed to participate and met the criteria. The OF was evaluated difficulty in chewing and swallowing, oral dryness, number of remaining teeth, and frequency of tooth brushing. Blood pressure was measured using an automatic digital blood pressure meter. Next-generation sequencing was used to analyze the gut microbiota. A two-way analysis of covariance revealed a significant interaction between the two OF groups and the two hypertension groups on Megamonas. The binomial logistic regression analysis stratified by OF revealed a positive correlation between Megamonas and hypertension (OR 1.317; P = 0.023). This cross-sectional epidemiological study of the local residents revealed that the abundance of Megamonas in the OF group was significantly higher in the hypertension group than in the normotension group; however, no such relationship was observed in the non-OF group.

Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein–protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2–Grin2b–Cdkl5–Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell–cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.

INTRODUCTION: The relationship between chronic pain (CP) and mortality among the Japanese elderly population remains unclear due to limited literature. OBJECTIVES: This study aimed to investigate the relationship between CP and mortality, stratified by age and sex, using longitudinal cohort data from the Shika Study. METHODS: This was a longitudinal study with 2849 participants aged ≥40 years (44.75% males and 55.25% females). Chronic pain, age, sex, tobacco smoking, height, and weight and self-reported information on medical conditions such as hypertension, hyperlipidemia, and diabetes mellitus were assessed using a CP questionnaire. RESULTS: The baseline mean age (years) was 64.00 ± 12.21 for men and 65.44 ± 13.12 for women. Among all participants, the mortality rate was significantly higher in males than in females (12.40% vs 7.80%; P < 0.001). The mortality rates among those with chronic headache (alive = 1.40% vs dead = 9.10%; P = 0.004) and neck/shoulder/elbow/hand pain (alive = 15.50% vs dead = 31.80%; P = 0.038) were significantly higher among the dead group compared to those alive in women. The odds of mortality associated with chronic headache (9.238 [95% CI 1.729-49.352]; P = 0.009) and neck/shoulder/elbow/hand pain (adjusted odd ratio 2.586 [95% CI 1.012-6.608]; P = 0.047) were significantly higher in females aged ≤74 years but not in males. CONCLUSION: Chronic headache and neck/shoulder/elbow/hand pain were found to be independently associated with mortality irrespective of other covariates among Japanese rural women aged ≤74 years in the Shika town longitudinal cohort study, Japan. This study potentially highlights the public health importance and negative impact of CP in women aged ≤74 years.