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1.
Nat Commun ; 10(1): 4422, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562322

RESUMO

Genome-wide association studies (GWAS) have identified ~170 genetic loci associated with prostate cancer (PCa) risk, but most of them were identified in European populations. We here performed a GWAS and replication study using a large Japanese cohort (9,906 cases and 83,943 male controls) to identify novel susceptibility loci associated with PCa risk. We found 12 novel loci for PCa including rs1125927 (TMEM17, P = 3.95 × 10-16), rs73862213 (GATA2, P = 5.87 × 10-23), rs77911174 (ZMIZ1, P = 5.28 × 10-20), and rs138708 (SUN2, P = 1.13 × 10-15), seven of which had crucially low minor allele frequency in European population. Furthermore, we stratified the polygenic risk for Japanese PCa patients by using 82 SNPs, which were significantly associated with Japanese PCa risk in our study, and found that early onset cases and cases with family history of PCa were enriched in the genetically high-risk population. Our study provides important insight into genetic mechanisms of PCa and facilitates PCa risk stratification in Japanese population.

2.
Ann Rheum Dis ; 78(10): 1430-1437, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31289104

RESUMO

OBJECTIVE: The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. METHODS: We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). RESULTS: This new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p<5.0×10- 8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three 'gout vs AHUA GWAS'-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. CONCLUSIONS: This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals.

3.
Int J Sports Med ; 40(10): 670-677, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342477

RESUMO

Apoptosis-associated, speck-like protein containing a caspase recruitment domain (ASC) plays an important role in inflammatory cytokine synthesis in peripheral blood mononuclear cells (PBMCs), and the expression of ASC is suppressed by increased methylation of its CpG sites. The current study investigated the longitudinal association of replacing sedentary time with light-intensity physical activity (LPA) or moderate to vigorous-intensity physical activity (MVPA) on the ASC methylation in middle-aged people. We investigated 1 238 individuals who participated in baseline and 5-year follow-up surveys of a population-based cohort study. Sedentary, LPA and MVPA time were objectively measured using accelerometers. ASC methylation in PBMCs was measured by pyrosequencing. Using a multiple linear regression and employing an isotemporal substitution model, the longitudinal associations of changes in the sedentary time, LPA and MVPA on the changes in the ASC methylation were analyzed after adjusting for potential confounders. Substituting 60 min per day of LPA for sedentary time was associated with 1.17 times (95% confidence interval 1.07, 1.27) higher ASC methylation levels (mean of 7 CpG sites, P<0.001). However, such effects were not seen for MVPA. These results suggest that substituting LPA for sedentary time may be linked with increased (favorable) ASC methylation as a potential biomarker of systemic inflammation.

4.
Endocrine ; 64(3): 552-563, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31011988

RESUMO

PURPOSE: This study aimed to investigate independent relationships of daily non-exercise life activity and leisure-time exercise volume and intensity with the prevalence of metabolic syndrome and its traits in Japanese adults. METHODS: Data of 24,625 eligible subjects (12,709 men, 11,916 women) who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study were analyzed. Information about lifestyle characteristics was obtained from a questionnaire. Logistic regression analyses were performed to evaluate the independent associations of daily life activity as well as leisure-time exercise volume and intensity with the prevalence of metabolic syndrome and its traits by sex. RESULTS: Male subjects with higher daily life activity as well as with higher leisure-time exercise volume had a lower prevalence of metabolic syndrome, independently with each other. Female subjects with higher daily life activity also had a lower prevalence of metabolic syndrome. Particularly, male and female subjects with the highest daily life activity quartile showed considerably low odds ratios of 0.66 (95% CI, 0.53-0.81) and 0.64 (0.52-0.79), respectively, for low HDL-cholesterol even after the adjustment for BMI compared with the first quartile. Meanwhile, male subjects with the higher leisure-time exercise showed a quite lower prevalence of elevated triglycerides. Higher moderate-intensity exercise was more intensely associated with a lower prevalence of metabolic syndrome and some of its traits in both sexes. CONCLUSIONS: Our results suggest that higher daily life activity and higher moderate-intensity exercise may be independently associated with a lower risk of metabolic syndrome in Japanese adults.

5.
Sleep ; 42(6)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-30810208

RESUMO

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

6.
J Epidemiol ; 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30344199

RESUMO

BACKGROUND: Selection of test-negative controls takes less time and costs less than traditional control selection for evaluating vaccine effectiveness (VE). Here, rotavirus VE was evaluated using hospital controls and compared with test-negative controls to determine whether using the latter can substitute for the former. METHODS: We recorded gastroenteritis in children from 2 months to 2 years of age at six medical facilities in Saga City between January 4th and May 31st, 2014. Stools from all identified acute gastroenteritis patients were tested for rotavirus using immunochromatography. Rotavirus gastroenteritis (RVGE) cases had test-positive stool, whereas test-negative controls had gastroenteritis but no rotavirus infection; hospital controls were outpatients visiting the same facility for indications other than gastroenteritis. Vaccination status was verified by inspecting maternal and child health records, and demographic data were obtained from a questionnaire completed by the patients' guardians or from the medical records. Unconditional logistic regression analysis was used to adjust for possible confounding factors. RESULTS: Sixty-four RVGE cases, 260 test-negative controls, and 589 hospital controls were enrolled. The characteristics of the two control groups, including RV vaccination history, were similar. The RVGE cases were more likely to have used daycare services than children from either of the two control groups. The VE against RVGE estimated using hospital controls was 86.6% (95% confidence interval [CI], 55.9-96.0%), very similar to the VE using test-negative controls (84.9% [95% CI, 49.6-95.5%]). CONCLUSIONS: The estimated VE using test-negative controls and hospital controls is similar. Therefore, test-negative controls are considered appropriate for establishing VE.

7.
Med Sci Sports Exerc ; 50(12): 2433-2441, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30102679

RESUMO

PURPOSE: Although 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: We 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.

8.
Vaccine ; 36(34): 5187-5193, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30037664

RESUMO

BACKGROUND: Rotavirus (RV) vaccination has been available in Japan since November 2011, but is not yet part of Japan's national immunisation programs. There are insufficient data on vaccine effectiveness (VE) among Japanese children. METHODS: Between the months of January and May in 2014 and 2015, we conducted active surveillance of gastroenteritis among children at 14 medical facilities. Rectal swabs from all patients with diarrhoea or vomiting were tested for RV by immunochromatography, and positive specimens were genotyped. Demographic data and immunisation records were obtained from a questionnaire completed by their parents/guardians or medical records. A test-negative case-control design was used to examine vaccine effectiveness (VE) using unconditional logistic regression analysis adjusted for possible confounding factors. RESULTS: Among the 1519 eligible subjects (children with acute gastroenteritis symptoms aged ≥2 months to <3 y visiting medical facilities) recruited, 487 cases and 925 controls were enrolled. Cases had more severe symptoms than controls, requiring more intensive treatment, including intravenous rehydration or hospitalisation. VE against all rotavirus gastroenteritis (RVGE) was 80.0% (95% confidence interval [CI], 72.8-85.5%), and VEs against RV1 and RV5 were similar, at 80.6% (95%CI, 70.7-87.1%) for RV1 and 80.4% (95% CI, 69.1-87.6%) for RV5. Although VEs of both vaccines decreased with age, VEs against all RVGE were >70% up to 2 years after vaccination. VEs increased with severity of RVGE, and VE against severe RVGE, requiring intravenous rehydration or hospitalisation, was 97.3% (95% CI, 88.8-99.3%). VEs of RV1 and RV5 against G1P[8] and G2P[4] were comparable, at RV1, 89.8% (95% CI, 78.2-95.5%) and 78.3% (95% CI, 23.6-93.8%); and RV5, 85.8% (95% CI, 72.8-92.6%) and 88.1% (95% CI, 10.1-98.4%), respectively. CONCLUSIONS: Rotavirus vaccines were effective in preventing mild to severe RVGE, irrespective of vaccine type, time since vaccination, or RV genotype.

9.
Am J Nephrol ; 47(5): 304-316, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29779033

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a rapidly growing, worldwide public health problem. Recent advances in genome-wide-association studies (GWAS) revealed several genetic loci associated with renal function traits worldwide. METHODS: We investigated the association of genetic factors with the levels of serum creatinine (SCr) and the estimated glomerular filtration rate (eGFR) in Japanese population-based cohorts analyzing the GWAS imputed data with 11,221 subjects and 12,617,569 variants, and replicated the findings with the 148,829 hospital-based Japanese subjects. RESULTS: In the discovery phase, 28 variants within 4 loci (chromosome [chr] 2 with 8 variants including rs3770636 in the LDL receptor related protein 2 gene locus, on chr 5 with 2 variants including rs270184, chr 17 with 15 variants including rs3785837 in the BCAS3 gene locus, and chr 18 with 3 variants including rs74183647 in the nuclear factor of -activated T-cells 1 gene locus) reached the suggestive level of p < 1 × 10-6 in association with eGFR and SCr, and 2 variants on chr 4 (including rs78351985 in the microsomal triglyceride transfer protein gene locus) fulfilled the suggestive level in association with the risk of CKD. In the replication phase, 25 variants within 3 loci (chr 2 with 7 variants, chr 17 with 15 variants and chr 18 with 3 variants) in association with eGFR and SCr, and 2 variants on chr 4 associated with the risk of CKD became nominally statistically significant after Bonferroni correction, among which 15 variants on chr 17 and 3 variants on chr 18 reached genome-wide significance of p < 5 × 10-8 in the combined study meta-analysis. The associations of the loci on chr 2 and 18 with eGFR and SCr as well as that on chr 4 with CKD risk have not been previously reported in the Japanese and East Asian populations. CONCLUSION: Although the present GWAS of renal function traits included the largest sample of Japanese participants to date, we did not identify novel loci for renal traits. However, we identified the novel associations of the genetic loci on chr 2, 4, and 18 with renal function traits in the Japanese population, suggesting these are transethnic loci. Further investigations of these associations are expected to further validate our findings for the potential establishment of personalized prevention of renal disease in the Japanese and East Asian populations.

10.
Int J Mol Sci ; 19(3)2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29494521

RESUMO

The purpose of the current study was to examine the influence of single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-δ (PPAR-δ), PPAR-γ, and α2 isoforms of the catalytic subunit of AMP-activated protein kinase (PRKAA2) on the extent of changes in anthropometric indices and blood measurements through exercise-centered lifestyle intervention in middle-aged men. A total of 109 Japanese middle-aged male subjects (47.0 ± 0.4 years) participated in the baseline health checkup, 6-month exercise-centered lifestyle intervention, and second checkup conducted several months after the subject completed the intervention. The body mass index (BMI), waist circumference, and clinical measurements, including hemoglobin Alc (HbA1c), triglyceride (TG), alanine aminotransferase (ALT), and γ-glutamyl-transpeptidase (γ-GTP), were measured at the baseline and second checkup. The three SNPs of PPAR-δ A/G (rs2267668), PPAR-γ C/G (rs1801282), and PRKAA2 A/G (rs1418442) were determined. Blunted responses in the reduction in the BMI and waist circumference were observed in A/A carriers of PPAR-δ SNP compared with G allele carriers (all p < 0.05). The A/A carriers also displayed less-marked improvements in HbA1c, TG, ALT, and γ-GTP (all p < 0.05). The current results suggest that A/A carriers of PPAR-δ SNP (rs2267668) may enjoy fewer beneficial effects of exercise-centered lifestyle intervention on anthropometric indices and blood measurements.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Antropometria , Biomarcadores/sangue , Estilo de Vida , PPAR delta/genética , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Fatores Etários , Alelos , Exercício , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/etiologia , Fatores Sexuais
11.
Stress ; 21(3): 237-246, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402173

RESUMO

Inconsistent associations have been reported between perceived stress and C-reactive protein (CRP), a marker of systemic inflammation. We previously observed a male-specific inverse relationship between perceived stress and CRP in a cross-sectional study. In the present study, we examined the longitudinal association between changes in perceived stress and CRP, and further analyzed whether changes in coping strategies and social support modify this association. This study included 8454 participants in both a baseline survey and a follow-up survey 5 years later. Psychosocial measures (i.e. perceived stress, coping strategies, and social support) and CRP concentrations were measured by identical means in both surveys. Consistent with our previous findings, increased perceived stress was significantly associated with lower CRP in men (ptrend = .037), but not in women. Increased "emotional expression," a coping strategy, was also associated with lower CRP in women (ptrend = .024). Furthermore, interactions between perceived stress and a coping strategy (positive reappraisal) or social support on CRP were found in men (pinteraction = .007 and .038, respectively); the above inverse association between stress and CRP was not detected for participants with diminished positive reappraisal or social support. In conclusion, increases in perceived stress during a 5-year period were associated with decreases in CRP among healthy men, and the observed association was possibly modified by coping strategy or social support.

12.
Sci Rep ; 8(1): 1493, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29367735

RESUMO

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10-6). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10-6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10-16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

13.
Psychosom Med ; 80(1): 28-33, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28700458

RESUMO

OBJECTIVE: Psychosocial stress may influence the risk of disease through its association with oxidative DNA damage. We examined whether perceived stress and depressive symptoms were associated with urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG. METHODS: This cross-sectional study included 6517 individuals aged 45 to 74 years who participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort study. Perceived stress during the past year was measured using a self-report questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Urinary 8-OHdG concentrations were measured using a column switching high-pressure liquid chromatography system coupled to an electrochemical detector. RESULTS: Higher perceived stress was significantly associated with higher 8-OHdG (2.1% increase per one-category increase of stress; ptrend = .025), even after adjusting for sex, age, supplement use, psychosocial factors, psychotropic medication use, smoking, and body mass index. This association was modestly attenuated after further adjustment for physical activity, suggesting possible mediation or confounding by this factor. Depressive symptoms were not significantly associated with 8-OHdG. No significant interaction was detected between perceived stress and depressive symptoms on 8-OHdG. CONCLUSIONS: In a general Japanese population, we found a weak positive association between perceived stress and urinary excretion of 8-OHdG, whereas no association was observed between depressive symptoms and 8-OHdG. Further studies are needed to examine whether the association between perceived stress and 8-OHdG is modified by depressive symptoms.

14.
Br J Nutr ; 118(6): 463-472, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28980890

RESUMO

Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.


Assuntos
Aromatase/genética , Grupo com Ancestrais do Continente Asiático/genética , Dieta , Estradiol Desidrogenases/genética , Estrogênios/sangue , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/sangue , Idoso , Animais , Estudos Transversais , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas na Dieta/administração & dosagem , Estradiol/sangue , Ácidos Graxos/administração & dosagem , Ácidos Graxos/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Feminino , Peixes , Técnicas de Genotipagem , Humanos , Japão , Estilo de Vida , Modelos Lineares , Pessoa de Meia-Idade , Alimentos Marinhos , Inquéritos e Questionários
15.
Artigo em Inglês | MEDLINE | ID: mdl-28515794

RESUMO

BACKGROUND: A low urine pH is a characteristic metabolic feature of metabolic syndrome and type 2 diabetes. The purpose of the current study was to investigate the effects of a 12-week home-based bench step exercise on the urine pH status of elderly female subjects. METHODS: The current study is a secondary analysis of a randomized controlled trial (RCT) in which 59 postmenopausal female subjects were randomized to either the exercise group (n = 29) or the control group (n = 30). The subjects in the exercise group were instructed to perform home-based exercises using a bench step at the anaerobic threshold (AT), with a goal of performing ≥140 min/week at home for 12 weeks. The subjects in the control group were instructed to not change their normal lifestyle. Urine was collected after overnight fasting, and the urine pH was measured using a urinary test strip. The inter-group-differences at baseline and the pre-post changes within groups were assessed using the Mann-Whitney U test and Wilcoxon's signed-rank test, respectively. Additionally, the difference in the post-intervention urine pH levels of the two groups, adjusted for the pre-intervention values (the estimated effect size) and the precision (95% confidence intervals) were investigated using an analysis of covariance. RESULTS: The pre-post comparison of the urine pH data using Wilcoxon's signed-rank test showed a significant increase in the urine pH levels of the exercise group (p < 0.05); there was no significant change in the urine pH levels of the control group. However, the estimated effect size (0.15) was small and the confidence interval straddled 0 (-0.25-0.55). CONCLUSIONS: Based on the results of the current secondary analysis of an RCT, we could not clearly conclude that exercise has a beneficial effect on the urine pH. Further well-designed RCTs should be conducted to determine whether aerobic exercise is truly able to ameliorate urine acidification. TRIAL REGISTRATION: The study was retrospectively registered in the University Hospital Medical Information Network (UMIN) as "Effect of step exercise on aerobic fitness and progression of atherosclerosis in the elderly" under the registration number UMIN 000026743 (the date of registration: March 28, 2017).

16.
Hepatol Res ; 47(3): E193-E200, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27219825

RESUMO

AIM: The aim of the current study is to examine whether home-based step exercise at anaerobic threshold (AT) and branched-chain amino acid (BCAA) supplementation improve aerobic capacity, ectopic fat in liver and muscle, and glycemic control in patients with liver cirrhosis. METHODS: Six female patients with compensated liver cirrhosis received oral BCAA and were instructed to undertake bench step exercises at an intensity that corresponded to AT, with a goal of performing 140 min of exercise per week at home for 12 months. Fat deposition in liver (liver to spleen ratio) and intramuscular adipose tissue content were assessed at baseline and after 6 and 12 months by computed tomography. Glycemic control indices (homeostasis model assessment of insulin resistance, hemoglobin A1c [HbA1c ], glycated albumin [GA] and chronic liver disease [CLD]-HbA1c [average of HbA1c and GA/3]) were also measured. RESULTS: Twelve months of moderate training significantly increased AT, which is an index of aerobic capacity, but no changes were observed in body weight, liver to spleen ratio, or intramuscular adipose tissue content. Glycated albumin significantly decreased (P < 0.05) and there tended to be a similar decrease in CLD-HbA1c (P < 0.1) after the exercise. The baseline serum triglyceride level correlated with changes in GA (P < 0.01) and CLD-HbA1c (P < 0.1). CONCLUSION: The current results suggest that the combination of home-based step exercise at AT and BCAA supplementation enhances aerobic capacity and potentially improves glycemic control in patients with cirrhosis without changes in body weight. The baseline serum serum triglyceride may partially explain the degree of improvement in glycemic control with exercise and BCAA intervention.

17.
Nutrients ; 8(9)2016 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-27608039

RESUMO

Interactions between dietary patterns and 2 ß-adrenergic receptor (ADRß) gene polymorphisms (ADRß2 Gln27Glu and ADRß3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35-69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRß3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRß polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRß3 polymorphism modifies the effects of the bread pattern on triglyceride levels.


Assuntos
Dieta , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 3/genética , Triglicerídeos/sangue , Adulto , Idoso , Alelos , Estudos de Coortes , Estudos Transversais , Feminino , Técnicas de Genotipagem , Heterozigoto , Homozigoto , Humanos , Japão , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Reprodutibilidade dos Testes , Inquéritos e Questionários
18.
Cancer Sci ; 107(11): 1653-1659, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27575995

RESUMO

Physical activity (PA) is recommended to both promote and maintain health and prevent cancer by improving the body's DNA repair system, which is considered a mechanism of cancer prevention. However, associations between PA and urinary levels of 8-hydroxydeoxyguanosine (8-OH-dG), which reflects DNA damage, are unclear. This cross-sectional study included 2370 men and 4052 women aged 45-74 years enrolled between 2010 and 2012. Habitual PA was assessed by single-axis accelerometer and urinary 8-OH-dG levels by automated HPLC. Multiple linear regression analysis was used to examine the relationship between log-transformed urinary 8-OH-dG and total PA (TPA) and PA of moderate/vigorous intensity (MVPA; ≥3 metabolic equivalents), with adjustment for age, body mass index, energy intake, alcohol consumption, smoking status, daily coffee drinking, menopause status (in women), and TPA (for MVPA). On multivariate adjustment, urinary 8-OH-dG levels were inversely correlated with TPA (ß = -0.020, P < 0.01) in women, and this correlation was not changed by PA intensity. Conversely, urinary 8-OH-dG levels were inversely correlated with MVPA (ß = -0.022, P < 0.05) in men, although the correlation with TPA was non-significant. This inverse correlation was clearer in current smokers than in never or former smokers, although the interaction between smoking status and MVPA on urinary 8-OH-dG levels was non-significant. In conclusion, greater TPA in women and greater MVPA in men were correlated with reduction in urinary 8-OH-dG, suggesting sex-specific effects of MVPA and TPA on protection from oxidative DNA damage. Increasing PA may mediate reduction in oxidative stress.


Assuntos
Desoxiguanosina/análogos & derivados , Exercício/fisiologia , Estresse Oxidativo , Acelerometria , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Carcinogênese/metabolismo , Desoxiguanosina/urina , Ingestão de Energia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fumar/epidemiologia , Inquéritos e Questionários
19.
Prev Med Rep ; 3: 288-95, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27419029

RESUMO

OBJECTIVE: Inflammation is closely involved in the development of type 2 diabetes, and cigarette smoking acts as potent inducer of inflammation. We therefore investigated interactions between inflammation-related gene polymorphisms and cigarette smoking on glycated hemoglobin (HbA1c) in the Japanese general population. METHOD: We conducted a cross-sectional study using data collected from 2619 Japanese (1274 males and 1345 females) 40-69 years of age who participated in baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study (2005-2008). Eight polymorphisms in seven genes (interleukin [IL]-1ß, IL-2, IL-4, IL-8, IL-10, IL-13 and tumor necrosis factor-α) were determined using the Invader assay. The interactions of smoking and gene polymorphisms on HbA1c levels were analyzed using multiple linear and logistic regression models and analysis of covariance with adjustment for potential confounders. RESULTS: Among the eight polymorphisms, only one significant interaction was detected for IL-1ß T-31C (P < 0.0001). Among the subjects carrying TT genotype, current heavy smokers (≥ 20 cigarettes/day) had higher HbA1c (5.83 [95% confidence interval 5.67-5.99] %) versus all other smoking status groups (never 5.49 [5.41-5.56] %, former 5.54 [5.43-5.65] %, current moderate [< 20 cigarettes/day] 5.50 [5.30-5.69] %), whereas such differences were not observed in the subjects with C allele. The logistic regression analyses regarding high-normal HbA1c levels showed a similar pattern of results. CONCLUSION: Smoking status did not interact with any other inflammation-related polymorphisms except for IL-1ß T-31C. Heavy smokers harboring the TT genotype of IL-1ß T-31C polymorphism show a greater adverse effect of smoking on HbA1c levels among Japanese middle-aged subjects.

20.
Hum Vaccin Immunother ; 12(5): 1244-9, 2016 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-26680277

RESUMO

Rotavirus gastroenteritis is a highly contagious, acute viral disease that imposes a significant health burden worldwide. In Japan, rotavirus vaccines have been commercially available since 2011 for voluntary vaccination, but vaccine coverage and effectiveness have not been evaluated. In the absence of a vaccination registry in Japan, vaccination coverage in the general population was estimated according to the number of vaccines supplied by the manufacturer, the number of children who received financial support for vaccination, and the size of the target population. Patients with rotavirus gastroenteritis were identified by reviewing the medical records of all children who consulted 6 major hospitals in Saga Prefecture with gastroenteritis symptoms. Vaccination status among these patients was investigated by reviewing their medical records or interviewing their guardians by telephone. Vaccine effectiveness was determined using a screening method. Vaccination coverage increased with time, and it was 2-times higher in municipalities where the vaccination fee was supported. In the 2012/13 season, vaccination coverage in Saga Prefecture was 14.9% whereas the proportion of patients vaccinated was 5.1% among those with clinically diagnosed rotavirus gastroenteritis and 1.9% among those hospitalized for rotavirus gastroenteritis. Thus, vaccine effectiveness was estimated as 69.5% and 88.8%, respectively. This is the first study to evaluate rotavirus vaccination coverage and effectiveness in Japan since vaccination began.


Assuntos
Gastroenterite/prevenção & controle , Programas de Imunização , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Vacinação , Feminino , Gastroenterite/diagnóstico , Hospitalização/estatística & dados numéricos , Humanos , Programas de Imunização/economia , Programas de Imunização/estatística & dados numéricos , Lactente , Japão , Masculino , Registros Médicos , Rotavirus/imunologia , Rotavirus/fisiologia , Infecções por Rotavirus/diagnóstico , Vacinação/economia , Vacinação/estatística & dados numéricos , Vacinas Atenuadas/administração & dosagem
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