Abstract
Background
Lifestyle modification is recommended for subjects with trace proteinuria during health checkups. However, whether overall healthy lifestyle reduces the incidence of ...trace/positive proteinuria or rapid decline in estimated glomerular filtration rate (eGFR) is not clarified.
Methods
A total of 451 534 people (277 494 men and 174 040 women) ages 20–79 years with negative proteinuria were included. The number of three healthy lifestyle factors (LFs) was assessed: noncurrent smoking, healthy eating habits (late dinner, snacking and skipping breakfast <3 times/week) and body mass index <25. The incidence of trace (±) and positive (≥1+) proteinuria by the dipstick method and eGFR decline ≥20% over 2 years were compared with the number of healthy LFs.
Results
The incidence of trace/positive proteinuria and rapid eGFR decline decreased with an increasing number of healthy LFs as follows: odds ratios (ORs) for trace proteinuria, 0.91 95% confidence interval (CI) 0.86–0.96, 0.82 (0.78–0.87) and 0.72 (0.68–0.77); ORs for positive proteinuria, 0.76 (95% CI 0.67–0.86), 0.56 (0.50–0.63) and 0.46 (0.40–0.53); and ORs for an eGFR decline ≥20%, 0.93 (95% CI 0.82–1.05), 0.90 (0.79–1.02) and 0.81 (0.70–0.93) for those with one, two and three healthy LFs compared with those with none of the three healthy LFs, respectively. Overall, subjects with a healthy lifestyle showed 28, 54 and 19% reduced risk of developing trace proteinuria, positive proteinuria and eGFR decline ≥20%, respectively, compared with those with an unhealthy lifestyle after 2 years. This association was similarly observed even among subjects without hypertension (HT) or diabetes mellitus (DM).
Conclusions
Subjects with an overall healthy lifestyle showed a lower incidence of trace/positive proteinuria by dipstick test and rapid eGFR decline over 2 years in a nationwide general population. Thus lifestyle modification should be recommended for subjects with trace proteinuria during health checkups, even for subjects without HT or DM.
Graphical Abstract
Abstract
Objectives
Up to 0.3% of Japanese have hypouricaemia. Most cases appear to result from a hereditary disease, renal hypouricaemia (RHUC), which causes exercise-induced acute kidney injury and ...urolithiasis. However, to what extent RHUC accounts for hypouricaemia is not known. We therefore investigated its frequency and evaluated its risks by genotyping a general Japanese population.
Methods
A cohort of 4993 Japanese was examined by genotyping the non-functional variants R90H (rs121907896) and W258X (rs121907892) of URAT1/SLC22A12, the two most common causative variants of RHUC in Japanese.
Results
Participants’ fractional excretion of uric acid and risk allele frequencies markedly increased at lower serum uric acid (SUA) levels. Ten participants (0.200%) had an SUA level ≤2.0 mg/dl and nine had R90H or W258X and were likely to have RHUC. Logistic regression analysis revealed these URAT1 variants to be significantly and independently associated with the risk of hypouricaemia and mild hypouricaemia (SUA ≤3.0 mg/dl) as well as sex, age and BMI, but these URAT1 variants were the only risks in the hypouricaemia population (SUA ≤2.0 mg/dl). W258X was only a risk in males with SUA ≤3.0 mg/dl.
Conclusion
Our study accurately reveals the prevalence of RHUC and provides genetic evidence for its definition (SUA ≤2.0 mg/dl). We also show that individuals with SUA ≤3.0 mg/dl, especially males, are prone to RHUC. Our findings will help to promote a better epidemiological understanding of RHUC as well as more accurate diagnosis, especially in males with mild hypouricaemia.
This study aimed to clarify the association of daily physical activity and leisure-time exercise with the risk of dysphagia in community-dwelling Japanese older adults using a questionnaire-based ...survey. We analyzed 3070 participants (1657 men, 1413 women; age 66 ± 4 years mean ± SD) of the Shizuoka and Daiko studies within the Japanese Multi-Institutional Collaborative Cohort study. We used the Dysphagia Risk Assessment for the Community-dwelling Elderly questionnaire to assess dysphagia risk and the International Physical Activity Questionnaire to assess daily physical activity and leisure-time exercise. Logistic regression analyses were used to evaluate the independent association of the amount of physical activity and leisure-time exercise with dysphagia risk. The proportion of participants with dysphagia risk was 27.5% (n = 844) and the risk was significantly higher in women (29.8%, n = 421) than in men (25.5%, n = 423; P = 0.008). Daily physical activity was not associated with dysphagia risk. A greater amount of leisure-time exercise was associated with lower dysphagia risk (P for trend = 0.003) and individuals in the highest leisure-time exercise quartile had a significantly lower odds ratio (0.68, 95% CI 0.52-0.89) than those in the lowest quartile, even after adjusting for the covariates.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene–environment interactions in lifestyle-related diseases, including cancers, among the ...Japanese. This report describes the study design and baseline profile of the study participants.Methods: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples.Results: The baseline survey included 92,610 adults (mean age: 55.2 standard deviation, 9.4 years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65–69 years for men and 60–64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women.Conclusions: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Development of correct topographical connections between peripheral receptors and central somatosensory stations requires activity-dependent synapse refinement, in which the NMDA type of glutamate ...receptors plays a key role. Here we compared functional roles of GluN2B (GluRε2 or NR2B) and GluN2D (GluRε4 or NR2D), two major regulatory subunits of neonatal NMDA receptors, in development of whisker-related patterning at trigeminal relay stations. Compared with control littermates, both the appearance of whisker-related patterning and the termination of the critical period, as assessed by unilateral infraorbital nerve transection, were delayed by nearly a day in the somatosensory cortex of GluN2B(+/-) mice but advanced by nearly a day in GluN2D(-/-) mice. Similar temporal shifts were found at subcortical relay stations in the thalamus and brainstem of GluN2B(+/-) and GluN2D(-/-) mice. In comparison, the magnitude of lesion-induced critical period plasticity in the somatosensory cortex, as assessed following row-C whisker removal, was normal in both mutants. Thus, GluN2B and GluN2D play counteractive roles in temporal development and maturation of somatosensory maps without affecting the magnitude of critical period plasticity. To understand the opposing action, we then examined neuronal and synaptic expressions of the two subunits along the trigeminal pathway. At each trigeminal station, GluN2B was predominant at asymmetrical synapses of non-GABAergic neurons, whereas GluN2D was selective to asymmetrical synapses of GABAergic neurons. Together, our findings suggest that GluN2B expressed at glutamatergic synapses on glutamatergic projection neurons facilitates refinement of ascending pathway synapses directly, whereas GluN2D expressed at glutamatergic synapses on GABAergic interneurons delays it indirectly.
Gout based on hyperuricemia is a common disease with a genetic predisposition, which causes acute arthritis. The ABCG2/BCRP gene, located in a gout-susceptibility locus on chromosome 4q, has been ...identified by recent genome-wide association studies of serum uric acid concentrations and gout. Urate transport assays demonstrated that ABCG2 is a high-capacity urate secretion transporter. Sequencing of the ABCG2 gene in 90 hyperuricemia patients revealed several nonfunctional ABCG2 mutations, including Q126X. Quantitative trait locus analysis of 739 individuals showed that a common dysfunctional variant of ABCG2, Q141K, increases serum uric acid. Q126X is assigned to the different disease haplotype from Q141K and increases gout risk, conferring an odds ratio of 5.97. Furthermore, 10% of gout patients (16 out of 159 cases) had genotype combinations resulting in more than 75% reduction of ABCG2 function (odds ratio, 25.8). Our findings indicate that nonfunctional variants of ABCG2 essentially block gut and renal urate excretion and cause gout.
•Defect of Hexb leads to change in sox2 gene in embryonic cortices.•Defect of Hexb leads to reduced neuronal precursor migration in embryonic cortices.•The production of layer-specific neurons is ...delayed in cortices of hexb−/− mice.
Sandhoff disease (SD) is a genetic disorder caused by a mutation of HEXB, which is the β-subunit gene of β-hexosaminidase A and B (HexA and HexB) in humans. HEXB mutation reduces HexA and HexB enzymatic activities, and results in the massive accumulation of ganglioside GM2 in the nervous system. Severe phenotypes of SD show progressive neurodegeneration in human infants, and lysosomal dysfunction that may affect the early development of the nervous system. In a previous study, neural stem cells (NSCs) and induced pluripotent stem cells derived from SD model mice, which are Hexb-deficient (Hexb−/−), demonstrated impaired neuronal differentiation. This study investigated early neurodevelopment in vivo using Hexb−/− mice. The structure of adult cerebral cortices of Hexb−/− mice was normal. However, the expression of Sox2, an NSC-related gene, was reduced in the embryonic cerebral cortices of Hexb−/− mice. Moreover, a reduction of early neuronal migration and differentiation was observed in the embryonic cerebral cortices of Hexb−/− mice. In addition, we showed that the production of layer-specific neurons was delayed in somatosensory cerebral cortices of Hexb−/− mice. These findings suggest that the alterations observed in embryonic Hexb−/− mice may contribute to deficits in neurodevelopment of SD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the ...associations depend on age.
The present cross-sectional study included 11,118 women, aged 35-69 years. Participants' longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis.
Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose-response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval CI: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old.
Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PURPOSEAlthough several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication ...studies have produced inconsistent results.
METHODSWe conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study.
RESULTSWe found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples.
CONCLUSIONSWe identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.
Purpose
The association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and ...metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population.
Methods
We used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35–69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined.
Results
During an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04–2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78–1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (
P
<0.05).
Conclusion
MetS diagnosed using the JASSO criteria and MUHO were associated with an increased risk of total cancer mortality in the Japanese population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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