Background: With the increasing burden of metabolic syndrome, it is crucial to focus on lifestyle interventions to reduce the risk. Diet is a modifiable factor that can reduce the risk of metabolic syndrome. Methods: We examined the association between the dietary diversity score (DDS) and risk of metabolic syndrome using baseline data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. In total, 75,332 participants were included in this study. A multiple logistic regression analysis was conducted to analyze the association between the DDS and metabolic syndrome. Results: Inverse associations were observed between a high DDS and metabolic syndrome (adjusted odds ratio, 0.83 [95% confidential interval 0.76-0.92]). Likewise, a high DDS was associated with reduced odds of a high body mass index and hypertension. No significant associations were observed between the DDS and serum triglyceride, fasting blood glucose, or high-density lipoprotein cholesterol values. Conclusion: To reduce the risk of metabolic syndrome, public health interventions should focus on promoting a diverse and balanced diet.
Background: The efficacy of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reported to be low in the elderly, partially owing to immunosenescence induced by a decrease in mitochondrial DNA (mtDNA). We aimed to evaluate the association between mtDNA levels in peripheral leukocytes and immune response against the SRAS-CoV-2 vaccine.Methods: A total of 210 participants (median age 79.5 years, 147 women) consisted of 83 nursing home residents or inpatients of long-term care units older than 60 years (Frail group), 70 outpatients more aged than 60 years (Robust group), and 57 younger than 60 years (Young group), was analyzed. Anti-spike IgG antibody (IgG(S)) titers were serially evaluated from before the first vaccination to six months after the third vaccination. We measured mtDNA levels in 45 elderly and cell-mediated immunity against SARS-CoV-2 in 22 elderly two months after the third vaccination.Findings: IgG(S) titers were consistently higher in the Robust group than in the Frail group. Significant but weak positive correlations were found between mtDNA levels and IgG(S) titers one and two months after the second vaccination (r=0.41 and 0.34, P<0.01 and P=0.02, respectively). In addition, a significant positive correlation was found between mtDNA levels and cell-mediated immunity (r=0.50 and P=0.02).Interpretation: Our data indicate that mtDNA levels in peripheral leukocytes are positively associated with vaccine-induced immunity. Further studies for therapeutic approaches to maintaining mtDNA levels can provide critical insights into immunosenescence in the elderly. Funding: There was no funding source for this study.Declaration of Interests: None.Ethics Approval: This study was carried out in accordance with the principles of the Declaration of Helsinki, as revised in 2008. This study was approved by the Haradoi Hospital institutional ethics review committee prior to data collection (Approval No. 2020-08), and all participants provided written informed consent prior to enrollment.
Introduction: Nonalcoholic fatty liver disease (NAFLD) genetic risk alleles are associated with lipid metabolism. However, the association between those variants and atherosclerosis has not yet been fully evaluated. Hypothesis: We hypothesized that NAFLD risk alleles are associated with the progression of atherosclerosis. Methods: A total of 1,150 Japanese men and women (median age 55 years) free of CVD, dyslipidemia, hypertension, and diabetes were studied. As NAFLD risk SNPs, variants of patatin-like phospholipase domain containing 3 ( PNPLA3 ), transmembrane 6 superfamily member 2 ( TM6SF2 ), glucokinase regulator ( GCKR ), and neurocan ( NCAN ) were assessed. Plasma total cholesterol, LDL cholesterol, small dense LDL cholesterol, LDL-triglycerides, HDL cholesterol, triglycerides, remnant-like particle cholesterol (RLP-C), fasting blood glucose (FBS), HbA1c, and high sensitivity CRP (hsCRP) were also measured. At baseline and after a five-year follow-up, carotid intima-media thickness (cIMT) was assessed using ultrasonography. Atherosclerosis was defined as cIMT over 1.1mm or the presence of a plaque. Univariate and multivariate analyses and chi-square and Fisher’s exact tests were performed to examine the associations between NAFLD risk SNPs, lipoproteins, and the progression of atherosclerosis. Results: Among 944 participants without atherosclerosis at baseline, the rate of plaque development was 13.1%, with the major allele (CC) of NCAN being significantly higher than non-CC alleles (13.8% vs. 4.7%, P = 0.04, Fisher’s exact test). Participants with the non-CC alleles of NCAN had significantly lower RLP-C at baseline than those with the CC allele (7.6 vs. 10.5 mg/dl, P = 0.02). In addition, participants with the non-CC alleles of NCAN had favorable metabolic parameters, lower blood pressure, triglycerides, small dense LDL cholesterol, and hsCRP, and higher HDL cholesterol than those with the CC allele (not significant). Conclusions: A NCAN variant, one of the NAFLD risk SNPs, was associated with plaque development among healthy Japanese participants, possibly mediated by favorable metabolism induced by the minor allele of NCAN .
An East Asian–specific variant on aldehyde dehydrogenase 2 ( ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci ( GCKR , KLB , and ADH1B ) in wild-type homozygotes and six ( GCKR , ADH1B , ALDH1B1 , ALDH1A1 , ALDH2 , and GOT2 ) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four ( GCKR , ADH1B , ALDH1A1 , and ALDH2 ) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.
The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m2 , the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m2 were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m2 were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m2 revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m2 , with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.
Many countries are administering a third dose of some coronavirus disease 2019 (COVID-19) vaccines, but the evaluation of vaccine-induced immunity after boosting in East Asia is insufficient. This study aimed to evaluate anti-spike immunoglobulin G [IgG(S)] titers after the third BNT162b2 vaccination.The dynamics of IgG(S) titers were assessed two months following the third BNT162b2 vaccination in 52 participants. All participants received the primary series of vaccination with BNT162b2 and received the third dose eight months after the second vaccination. Associations among the IgG(S) titer, baseline characteristics, and adverse reactions were also evaluated.The geometric mean titer of IgG(S) one month after the third vaccination was 17,400 AU/ml, which increased by approximately 30 times that immediately before the third vaccination. The rate of IgG(S) titer decline was significantly slower after the third vaccination (35.7%) than after the second vaccination (59.1%). The IgG(S) titer was significantly negatively associated with age (r = -0.31). Participants who had a headache at the time of vaccination showed significantly higher IgG(S) titers than those without a headache.The IgG(S) titer induced by primary immunization with BNT162b2 waned over time. The third dose of BNT162b2 substantially increased the IgG(S) titer, with a slower rate of decline.
Abstract BACKGROUND Increases in circulating LDL cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) concentrations are significant risk factors for cardiovascular disease (CVD). We assessed direct LDL-C and hsCRP concentrations compared to standard risk factors in the Framingham Offspring Study. METHODS We used stored frozen plasma samples (−80 °C) obtained after an overnight fast from 3147 male and female participants (mean age, 58 years) free of CVD at cycle 6 of the Framingham Offspring Study. Overall, 677 participants (21.5%) had a CVD end point over a median of 16.0 years of follow-up. Total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), direct LDL-C (Denka Seiken and Kyowa Medex methods), and hsCRP (Dade Behring method) concentrations were measured by automated analysis. LDL-C was also calculated by both the Friedewald and Martin methods. RESULTS Considering all CVD outcomes on univariate analysis, significant factors included standard risk factors (age, hypertension, HDL-C, hypertension treatment, sex, diabetes, smoking, and TC concentration) and nonstandard risk factors (non-HDL-C, direct LDL-C and calculated LDL-C, TG, and hsCRP concentrations). On multivariate analysis, only the Denka Seiken direct LDL-C and the Dade Behring hsCRP were still significant on Cox regression analysis and improved the net risk reclassification index, but with modest effects. Discordance analysis confirmed the benefit of the Denka Seiken direct LDL-C method for prospective hard CVD endpoints (new-onset myocardial infarction, stroke, and/or CVD death). CONCLUSIONS Our data indicate that the Denka Seiken direct LDL-C and Dade Behring hsCRP measurements add significant, but modest, information about CVD risk, compared to standard risk factors and/or calculated LDL-C.
AbstractPurpose:The impact of diet on the body acid-base balance may be related to the risk of various chronic diseases. Despite emerging evidence on the relationships between the dietary acid load and all-cause and cause-specific mortalities, further information is needed. This prospective cohort study examined the relationships between the dietary acid load and all-cause and cause-specific mortalities in a large Japanese population. Methods: The data of 74,360 subjects (aged 35-69 years in the baseline survey) in the Japan Multi-Institutional Collaborative Cohort Study were analyzed. The dietary acid load was estimated using the net endogenous acid production (NEAP) score. Cox proportional hazards regression analyses were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortalities according to the quartiles of the energy-adjusted NEAP score after adjustments for potential confounders. Sex-stratified analyses were also conducted. Results: During a mean follow-up of 11.6 years, 3,761 deaths (2,467 male and 1,294 female subjects) were identified. A higher NEAP score was associated with higher all-cause mortality (HR 1.16, 95% CI 1.04-1.28) and cerebrovascular disease mortality (HR 1.69, 95% CI 1.08-2.65). Sex-stratified analyses showed that the NEAP score was associated with all-cause and cause-specific mortalities, including cerebrovascular disease mortality (HR 2.32, 95% CI 1.23 - 4.40), in male subjects, but not in female subjects. Conclusion: The present results suggest that the dietary acid load is associated with a higher risk of all-cause and cause-specific mortalities, including cerebrovascular death, in Japanese male adults.
