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1.
Nagoya J Med Sci ; 83(1): 183-194, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33727749

RESUMO

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P <5×10-8), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance (P <1×10-6). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SGMS2 SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of KLK3 SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future.

2.
Br J Nutr ; : 1-9, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33632354

RESUMO

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1-3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.

3.
Arch Osteoporos ; 16(1): 30, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580354

RESUMO

In Kyoto Prefecture, Japan, the number of hip fractures increased during 2013-2017 compared to 2008-2012. However, the estimated overall incidence rate increased only in femoral neck fractures in men aged ≥75 and women aged ≥85. PURPOSE: The incidence rate of hip fractures in Japan has plateaued or decreased. We investigated the annual hip fracture occurrences in Kyoto Prefecture, Japan, from 2008 to 2017. METHODS: Patients aged 65 years and above who sustained hip fractures between 2008 and 2017 and were treated at one of the participating 11 hospitals were included. The total number of beds in these institutions was 3701, accounting for 21.5% of the 17,242 acute-care beds in Kyoto Prefecture. The change in incidence rate was estimated utilizing the population according to the national census conducted in 2010 and 2015. RESULTS: The total number of hip fractures was 10,060, with 47.5% femoral neck fractures and 52.5% trochanteric fractures. A decrease in number was seen only in trochanteric fractures in the group of 75- to 84-year-old women. The population-adjusted numbers of femoral neck fractures showed a significant increase in all age groups in men, whereas in women, there was an increase in femoral neck fractures in the ≥85 group and trochanteric fractures in the age group 65-74, and a decrease in trochanteric fractures in the age group 75-84. The estimated change in incidence rate showed an increase in femoral neck fractures in men aged ≥75 and women aged ≥85. CONCLUSION: In Kyoto Prefecture, the number of hip fractures increased in the second half of the study period (2013-2017) compared to the first half (2008-2012). However, the incidence rate had not increased, except in femoral neck fractures in men aged ≥75 and women aged ≥85.


Assuntos
Fraturas do Colo Femoral , Fraturas do Quadril , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Colo Femoral/epidemiologia , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Japão/epidemiologia , Masculino
4.
Healthcare (Basel) ; 9(2)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546229

RESUMO

The relationship between Helicobacter pylori infection and/or gastric disorders and chronic kidney disease (CKD) has not been elucidated. We investigated the relationship between Helicobacter pylori and/or atrophic gastritis (AG) and chronic kidney disease. In total, 3560 participants (1127 men and 2433 women) were eligible for this cross-sectional study. We divided participants into four study groups: with/without Helicobacter pylori infection and with/without AG. The HP (+) AG (-) group demonstrated a significant association with CKD compared with the HP (-) AG (-) group (adjusted odds ratio, 1.443; 95% confidence interval, 1.047-1.989). In contrast, the HP (+) AG (+) group showed significantly lower adjusted odds of CKD than the HP (-) AG (-) group (adjusted odds ratio, 0.608; 95% confidence interval, 0.402-0.920). H. pylori infection without AG might be associated with CKD in these participants. Conversely, the HP (+) AG (+) group had lower odds of CKD. Uncovering an association between gastric and renal conditions could lead to development of new treatment strategies.

5.
Neuroradiology ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599817

RESUMO

PURPOSE: Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs. METHODS: A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment. RESULTS: Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment. CONCLUSION: The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs.

6.
J Epidemiol ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33612706

RESUMO

BACKGROUND: Inflammation is thought to be a risk factor for kidney disease. However, discussion is controversial whether inflammatory status is either a cause or an outcome of chronic kidney disease. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using mendelian randomization (MR) approaches. METHODS: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively. RESULTS: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 95%CI: 0.000, -0.019 to 0.020 and -0.003, -0.019 to 0.014). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 95% CI: -0.005, -0.020 to 0.010 and -0.004, -0.020 to 0.012). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: -0.008, -0.058 to 0.042; IVAsian: 0.001, -0.036 to 0.036). CONCLUSIONS: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.

7.
Sci Rep ; 11(1): 305, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431996

RESUMO

We investigated the potential of mid-regional pro-adrenomedullin (MR-proADM) for use as a novel biomarker for arterial stiffness as the criterion for vascular failure and cardiometabolic disease (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome) compared with high-sensitivity C-reactive protein (hsCRP). Overall, 2169 individuals (702 men and 1467 women) were enrolled. Multiple regression analysis was performed to assess the association of MR-proADM and hsCRP with brachial-ankle pulse wave velocity (baPWV), adjusting for other variables. The diagnostic performance (accuracy) of MR-proADM with regard to the index of vascular failure was tested with the help of receiver operating characteristic curve analysis in the models. MR-proADM was significantly higher in participants with vascular failure, as defined by baPWV and/or its risk factors (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome), than in control groups. Independent of cardiovascular risk factors (age, drinking, smoking, body mass index, systolic blood pressure, lipid and glycol metabolism), MR-proADM was significantly associated with baPWV, and MR-proADM showed higher areas under the curve of baPWV than hsCRP showed. MR-proADM is more suitable for the diagnosis of higher arterial stiffness as the criterion for vascular failure than hsCRP. Because vascular assessment is important to mitigate the most significant modifiable cardiovascular risk factors, MR-proADM may be useful as a novel biomarker on routine blood examination.

8.
Neurol Med Chir (Tokyo) ; 61(2): 63-97, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33455998

RESUMO

Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.

9.
Obes Res Clin Pract ; 14(6): 531-535, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33168484

RESUMO

The association between health benefits and physical activity has received increasing attention among researchers working on the prevention of noncommunicable disease. However, the number of studies on the association between daytime activities and visceral fat is limited. In this study, we evaluated how daily physical activity behaviors impact the visceral adipose tissue (VAT) and body mass index (BMI). A total of 3543 participants (1240 men, 2303 women) were included in this cross-sectional study. The duration of daily physical activities (sedentary time, standing time, and walking time) was classified into the six categories. Multiple regression analysis was carried out to compare continuous variables. VAT and BMI were used as dependent variables, and the daily physical activities were used as independent variables. All results were expressed after adjusting for confounders, including sex, age, Brinkman index, daily alcohol consumption, sleeping time, and medication for hypertension, dyslipidemia, and diabetes. The multiple regression analysis showed that sedentary time was significantly associated with VAT (beta = 1.145, p value = 0.002), whereas standing time was negatively associated with VAT (beta = -0.763, p value = 0.043). Walking time was negatively and robustly associated with all depending variables as follows: BMI (beta = -0.172, p value = 0.001) and VAT (beta = -2.023, p value <0.001). This study showed that a daily behavior time affects the accumulation of VAT and BMI. A shift from sedentary time to standing or walking time might be a key population approach to prevent cardiometabolic diseases.

10.
J Bone Miner Metab ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044569

RESUMO

INTRODUCTION: Bone mass was recently reported to be related to skeletal muscle mass in humans, and a decrease in cortical bone is a risk factor for osteoporosis. Because circulating myostatin is a factor that primarily controls muscle metabolism, this study examined the role of myostatin in bone mass-skeletal muscle mass interactions. METHODS: The subjects were 375 middle-aged community residents with no history of osteoporosis or sarcopenia who participated in a health check-up. Cortical bone thickness and cancellous bone density were measured by ultrasonic bone densitometry in a health check-up survey. The subjects were divided into those with low cortical bone thickness (LCT) or low cancellous bone density (LBD) and those with normal values (NCT/NBD). Bone metabolism markers (TRACP-5b, etc.), skeletal muscle mass, serum myostatin levels, and lifestyle were then compared between the groups. RESULTS: The percentage of diabetic participants, TRACP-5b, and myostatin levels were significantly higher, and the frequency of physical activity, skeletal muscle mass, grip strength, and leg strength were significantly lower in the LCT group than in the NCT group. The odds ratio (OR) of high myostatin levels in the LCT group compared with the NCT group was significant (OR 2.17) even after adjusting for related factors. Between the low cancellous bone density (LBD) and normal cancellous bone density (NBD) groups, significant differences were observed in the same items as between the LCT and NCT groups, but no significant differences were observed in skeletal muscle mass and blood myostatin levels. The myostatin level was significantly negatively correlated with cortical bone thickness and skeletal muscle mass. CONCLUSIONS: A decrease in cortical bone thickness was associated with a decrease in skeletal muscle mass accompanied by an increase in the blood myostatin level. Blood myostatin may regulate the bone-skeletal muscle relationship and serve as a surrogate marker of bone metabolism, potentially linking muscle mass to bone structure.

11.
J Neurol Sci ; 419: 117166, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33065495

RESUMO

INTRODUCTION: Our previous community-based study demonstrated that some individuals with AVIM [asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus (iNPH) on magnetic resonance imaging (MRI)] progressed to iNPH in several years. In this hospital-based study, we investigated the progression rate from AVIM to iNPH and its possible predictors. METHODS: We conducted a prospective study of participants with AVIM from several medical institutions/hospitals in Japan. AVIM is defined as "asymptomatic ventriculomegaly with features of iNPH on MRI"; in the present study, asymptomatic was defined as "0 (no symptoms) or 1 (presence of only subjective, but not objective, symptoms) on the iNPH Grading Scale (iNPH-GS)." We also measured possible predicting factors for AVIM-to-iNPH progression, including age, sex, body weight, blood pressure, diabetes mellitus, dyslipidemia, history of mental disease/head injury/sinusitis/smoking/alcohol-intake, Evans index, and the presence of DESH (disproportionately enlarged subarachnoid-space hydrocephalus) findings on brain MRI, and analyzed these potential predictive values. RESULTS: In 2012, 93 participants with AVIM were registered and enrolled in the study. Of these, 52 participants were able to be tracked for three years (until 2015). Of the 52 participants, 27 (52%) developed iNPH during the follow-up period (11 definite, 6 probable, and 10 possible iNPH), whereas 25 participants remained asymptomatic in 2015. Among the possible predictive factors examined, the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression. CONCLUSIONS: The multicenter prospective study demonstrated that the progression rate from AVIM to iNPH was ~17% per year, and the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression.

12.
Bone ; 141: 115669, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33022454

RESUMO

BACKGROUND: The acquisition of a high bone density at a young age is a strategy to prevent fractures/falls later in life. We therefore decided to investigate the increases in cortical thickness (CoTh) and trabecular bone density (TBD) of children. METHODS: Subjects comprised 1314 students (678 boys and 636 girls) aged between 12 and 18 years. Lifestyle factors were examined with a self-administered questionnaire (sleep times, exercise habits, and calcium intake). Bone growth was assessed based on CoTh and TBD using an ultrasonic bone densitometer. Height, weight, and body fat percentage were also measured. RESULTS: Increases in CoTh and TBD occurred earlier in girls than in boys. Calcium intake was not sufficient at any of the ages examined, and sleep times were shorter than those recommended by the National Sleep Foundation. Increases in CoTh and TBD occurred subsequent to increases in height. Although increases in CoTh were observed with age in both sexes, TBD increased in boys until the age of 17 years and in girls until the age of 15 years. At 18 years of age, the young adult mean value was greater than 100% for CoTh but lower than 100% for TBD. A multivariate analysis identified age, body mass index (BMI), and exercise as independent positive factors for CoTh, while body fat percentage was an independent negative factor. Age and BMI were independent positive factors for TBD in both sexes, whereas body fat percentage was a positive factor in boys only. CONCLUSIONS: The study found that CoTH and TBD varied with age and differed in increase in boys and girls; related factors of bone increase could also be found. The results of this study may contribute to the acquisition of high bone density in children and adolescents.

13.
Nutrients ; 12(10)2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33050584

RESUMO

BACKGROUND: The study aimed to investigate the association between daily consumption of coffee or green tea, with and without habitual bread consumption for breakfast, and components and prevalence of metabolic syndrome in Japanese populations. METHODS: The study population consisted of 3539 participants (1239 males and 2300 females). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analyses to evaluate the associations of daily coffee and green tea consumption with the prevalence of obesity, visceral obesity, and metabolic syndrome. RESULTS: Coffee consumption was associated with significantly lower proportions of visceral obesity (OR: 0.746, CI: 0.588-0.947) and metabolic syndrome (OR: 0.706, CI: 0.565-0.882). On the other hand, green tea was not associated with visceral obesity (OR: 1.105, CI: 0.885-1.380) or metabolic syndrome (OR: 0.980, CI: 0.796-1.206). The combination of daily drinking coffee and eating bread at breakfast time was associated with significantly lower proportions of obesity (OR: 0.613, CI: 0.500-0.751) (p = 0.911 for interaction), visceral obesity (OR: 0.549, CI: 0.425-0.710) (p = 0.991 for interaction), and metabolic syndrome (OR: 0.586, CI: 0.464-0.741) (p = 0.792 for interaction). CONCLUSION: Coffee consumption was significantly associated with lower visceral adipose tissue and lower proportions of visceral obesity, but the same was not true for green tea consumption. Furthermore, in combination with coffee consumption, the addition of eating bread at breakfast time significantly lowered proportions of visceral obesity and metabolic syndrome, although there was no interaction between coffee and bread.

14.
Sci Rep ; 10(1): 18499, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116160

RESUMO

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B12 as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B12, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41-3.96) in men and 1.86 (95% CI 1.11-3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B12 was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B12.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32503285

RESUMO

BACKGROUND: The aim of this study was to investigate whether plasma midregional proadrenomedullin (MR-proADM) reflected body composition, such as body mass index (BMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), VAT/SAT ratio, body fat mass (BFM), and skeletal muscle mass (SMM). METHODS: A total of 2244 individuals (727 men and 1517 women) were included in the study. Multiple regression analysis was performed to assess the combined influence of variables: age, daily alcohol consumption, Brinkman index, sleeping time, metabolic equivalents, anamnesis for hypertension, dyslipidemia, diabetes, and body composition of MR-proADM, by using a stepwise forward selection method. RESULTS: MR-proADM was significantly related to all anthropometric indices (BMI, VAT, SAT, VAT/SAT ratio, BFM, and SMM) in men and women. On the basis of a stepwise forward selection method, VAT (men: beta = 0.184, p < 0.001, women: beta = 0.203, p < 0.001) and BFM (beta = 0.181, p < 0.001) in women, were found to be significantly associated with MR-proADM. CONCLUSION: This study suggests that plasma MR-proADM concentration is a more reliable indicator of VAT for fat distribution, and thus, MR-proADM may help better understand the obesity paradox. Changes in circulating levels of MR-proADM could possibly reflect changes in body composition, endocrine, and metabolic milieu.


Assuntos
Gordura Intra-Abdominal , Obesidade , Adrenomedulina , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas
16.
J Atheroscler Thromb ; 27(10): 1097-1107, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32269208

RESUMO

AIM: Accumulating evidence reveals that sedentary behavior is associated with mortality and cardiometabolic disease; however, there are potential age and sex differences in sedentary behavior and health outcomes that have not been adequately addressed. This study aimed to determine the association of sedentary behavior with cardiometabolic diseases such as hypertension, dyslipidemia, diabetes mellitus, and its risk factors in a large Japanese population according to age and sex. METHODS: Using data from the Japan Multi-Institutional Collaborative Cohort Study obtained from baseline surveys, data of 62,754 participants (27,930 males, 34,824 females) were analyzed. This study uses a cross-sectional design and self-administered questionnaires to evaluate sedentary time and anamnesis. For the logistic regression analysis, sedentary time <5 h/day was used as the reference and then adjusted for age, research areas, leisure-time metabolic equivalents, and alcohol and smoking status. From the analysis of anthropometric and blood examinations, 35,973 participants (17,109 males, 18,864 females) were analyzed. RESULTS: For hypertension and diabetes, sedentary time was associated with a significantly higher proportion of male participants. Both sexes were associated with a significantly higher proportion of participants with dyslipidemia. Participants who had longer sedentary time tended to have increased levels of blood pressure, triglycerides, and non-high-density lipoprotein cholesterol (HDL-C), and decreased levels of HDL-C, especially in the 60-69 years group. CONCLUSIONS: Independent of leisure-time physical activity, sedentary time was associated with cardiometabolic diseases in a large Japanese population classified by age and sex. Our findings indicate that regularly interrupting and replacing sedentary time may contribute to better physical health-related quality of life.

17.
Ann Rheum Dis ; 79(5): 657-665, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32238385

RESUMO

OBJECTIVES: Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000-3000 years. METHODS: Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. RESULTS: In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10-8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients' gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. CONCLUSIONS: Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Aldeído-Desidrogenase Mitocondrial/genética , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Gota/genética , Proteínas de Neoplasias/genética , Estudos de Casos e Controles , Loci Gênicos , Genótipo , Gota/epidemiologia , Humanos , Incidência , Japão , Masculino , Fenótipo , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença
18.
J Epidemiol ; 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32147644

RESUMO

BACKGROUND: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. METHODS: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20) and change in BMI (BMI change), among 11 586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. RESULTS: We found a significant association (P < 0.05/282 = 1.77×10-4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained even after additional adjustment for dietary energy intake. CONCLUSIONS: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.

19.
J Pharm Biomed Anal ; 183: 113168, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32062014

RESUMO

Mid-regional pro-adrenomedullin (MR-proADM) is suggested to be a prognostic indicator for various diseases. Plasma MR-proADM concentration is commonly measured using immunoassays based on its immunochemical characteristics. However, some immunological interactions affect the measured concentration. We developed and validated a sensitive and selective method for measuring plasma MR-proADM concentration using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and evaluated its clinical applicability. Plasma samples were prepared by protein precipitation and solid-phase extraction. Samples obtained from healthy volunteers (n = 38), patients with chronic kidney disease (CKD) stages 3 and 4-5 (non-dialysis; n = 20 and 17, respectively), and CKD stage 5D (dialysis; n = 34) were analyzed. Within-batch and batch-to-batch accuracy of the UPLC-MS/MS assay for quality control samples ranged from -0.69 % to 8.05 % and from 1.72 % to 5.76 %, respectively. The lower limit of quantification was 0.4 ng mL-1. The MR-proADM concentration determined using the UPLC-MS/MS assay correlated strongly with that determined using the immunoassay (Pearson's product-moment correlation coefficient [r] = 0.7875, p < 0.001). Median (range) plasma MR-proADM concentrations of healthy volunteers, patients with CKD stages 3 and 4-5, and patients with CKD stage 5D were 0.67 (0.43-1.27), 1.89 (0.65-6.68), 3.86 (1.60-8.75) and 3.97 (0.66-9.20) ng mL-1, respectively, and a significant difference among four groups was confirmed. We established a sensitive and selective method for determining plasma MR-proADM concentration using UPLC-MS/MS. Our novel UPLC-MS/MS assay for determining plasma MR-proADM concentration can be used in the clinical setting and may have better selectivity than the immunoassay method.

20.
Pediatr Int ; 62(6): 694-700, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31958354

RESUMO

BACKGROUND: The process of birth causes stress for neonates, but additional stressors for sick neonates are a matter of concern. As analysis of heart-rate variability (HRV), which reflects autonomic activity, has demonstrated that low-frequency (LF) activity reflects overall autonomic activity, high-frequency (HF) activity reflects parasympathetic activity, and the LF/HF ratio reflects sympathetic activity, HRV has been clinically applied as a non-invasive index of physical stress. In this study, we evaluated whether HRV is useful as a stress index for neonates by analyzing it in comparison with their salivary cortisol level. METHODS: We measured the salivary cortisol level and HRV in 12 healthy neonates and 37 neonates born during between 2014 and 2016 and admitted to the neonatal intensive care unit. These examinations were performed at birth and after approximately 1 week. The changes in parameters with time were examined. RESULTS: The LF and HF values in both groups exhibited significant negative correlations with the salivary cortisol level. In those admitted to the neonatal intensive care unit, the LF and HF values were correlated with gestational age and height. In the healthy neonates, a reduced salivary cortisol level and increase in the LF and HF values were observed approximately 1 week after birth compared with the values at birth, whereas the LF/HF ratio was not correlated with the salivary cortisol level and did not change over time. CONCLUSIONS: The LF and HF values were significantly correlated with the cortisol level, suggesting their usefulness as physiological indices of stress in clinical neonatal care.

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