Biomedical subjects

Yasuharu Tabara

Publications and source records attributed to Yasuharu Tabara.

At least 19 recordsLinked to original sources

PubMed2026

Association between orthostatic blood pressure change and masked and white coat hypertension: the Nagahama study.

BACKGROUND: Exaggerated blood pressure (BP) response to orthostatic stimuli is indicative of cardiovascular frailty and may be associated with masked and white coat hypertension, which are BP abnormalities associated with cardiovascular outcomes. We aimed to clarify this possible association in a cross-sectional analysis of a large general population. METHODS: We enrolled 7618 community residents (mean age: 57.7 years). Orthostatic BP change was calculated as the difference between systolic BP measured in a seated position and at 3 min after standing. Orthostatic hypertension and hypotension were defined as >20 mmHg increase or decrease in systolic BP, respectively. Masked and white coat hypertension were defined based on office and home morning BP measurements. RESULTS: The frequency of orthostatic hypotension and hypertension was 1.8% and 1.6%, respectively. A significant association was observed between orthostatic BP change and office-to-home BP differences, that is, the greater the increase in orthostatic BP, the higher the home BP than the office BP. The association between orthostatic hypertension and masked hypertension (crude odds ratio: 3.15; P  < 0.001) remained significant even after adjusting for potential covariates, including office seated BP. In addition, orthostatic hypotension was independently associated with white coat hypertension (crude odds ratio: 2.14; P  = 0.002). Orthostatic BP change measured at 3 min showed a clearer association with masked and white coat hypertension than that measured at 1 min. CONCLUSION: We identified a physiological association between exaggerated postural BP variability and office-to-home BP differences, which were previously considered unrelated.

Humans↗

PubMed2025

Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20 % of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels. RESULTS: The one-degree of freedom variant-sleep interaction test identified 10 novel loci (Pint<5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (Pjoint<5.0e-9 in combination with Pint<6.6e-6). Multiple loci, including those mapped to APSH (target for aspartic and succinic acid) and SLC8A1 showed biological plausibility and druggability potential based on literature. CONCLUSIONS: Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.

Humans↗

PubMed2025

Effects of room temperature on home morning, evening, and sleep blood pressure: the Shizuoka study.

BACKGROUND: Cold ambient temperatures are known to increase blood pressure (BP), but the influence of room temperature remains understudied. This study examined the impact of room temperature in morning, evening, and sleep BP measured at home. METHODS: The study included 779 adults (mean age: 70.7 years) from a community-based longitudinal study. Home BP was measured for 1 week using a conventional cuff-oscillometric device, whereas sleep BP was automatically recorded at 00 : 00, 02 : 00, and 04 : 00 using a timer-equipped BP monitor. Room temperature was measured concurrently using a thermometer in the BP monitor. RESULTS: A 1°C decrease in room temperature increased morning systolic and diastolic BPs by 0.863 and 0.342 mmHg, respectively ( P  < 0.001). The evening systolic and diastolic BPs increased by 0.721 and 0.320 mmHg, respectively ( P  < 0.001). However, sleep systolic (0.076 mmHg, P = 0.181) and diastolic (0.078 mmHg, P  = 0.039) BPs showed weaker associations. The association between morning systolic and diastolic BPs remained significant after adjusting for ambient temperature (0.809 and 0.304 mmHg, respectively; P  < 0.001). Age was the only factor associated with room temperature-related BP changes. Among 433 normotensive individuals (based on 1-week average morning BP), 93 were hypertensive on the coldest day. These participants had higher average morning BPs within the normal range and were more likely to use antihypertensive medication. CONCLUSION: Room temperature significantly influenced home morning and evening BPs but not sleep BP, independent of ambient temperature. Maintaining appropriate room temperatures may aid in BP management at home.

Humans↗

PubMed2006

The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease.

We scanned throughout chromosome 21 to assess genetic associations with late-onset Alzheimer disease (AD) using 374 Japanese patients and 375 population-based controls, because trisomy 21 is known to be associated with early deposition of beta-amyloid (Abeta) in the brain. Among 417 markers spanning 33 Mb, 22 markers showed associations with either the allele or the genotype frequency (P < 0.05). Logistic regression analysis with age, sex and apolipoprotein E (APOE)-epsilon4 dose supported genetic risk of 17 markers, of which eight markers were linked to the SAMSN1, PRSS7, NCAM2, RUNX1, DYRK1A and KCNJ6 genes. In logistic regression, the DYRK1A (dual-specificity tyrosine-regulated kinase 1A) gene, located in the Down syndrome critical region, showed the highest significance [OR = 2.99 (95% CI: 1.72-5.19), P = 0.001], whereas the RUNX1 gene showed a high odds ratio [OR = 23.3 (95% CI: 2.76-196.5), P = 0.038]. DYRK1A mRNA level in the hippocampus was significantly elevated in patients with AD when compared with pathological controls (P < 0.01). DYRK1A mRNA level was upregulated along with an increase in the Abeta-level in the brain of transgenic mice, overproducing Abeta at 9 months of age. In neuroblastoma cells, Abeta induced an increase in the DYRK1A transcript, which also led to tau phosphorylation at Thr212 under the overexpression of tau. Therefore, the upregulation of DYRK1A transcription results from Abeta loading, further leading to tau phosphorylation. Our result indicates that DYRK1A could be a key molecule bridging between beta-amyloid production and tau phosphorylation in AD.

Aged↗

PubMed2006

An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension.

Cold-induced autoinflammatory syndrome 1 (CIAS1) gene is a member of the NALP subfamily of the CATERPILLER protein family that is expressed predominantly in peripheral blood leukocytes, which is to regulate apoptosis or inflammation through the activation of NF-kappaB and caspase. Recent genetic analyses suggested an association between inflammation and oxidative stress-related genes in the development of hypertension. This is the first genetic study indicating an association between the CIAS1 gene and susceptibility to essential hypertension (EH). The frequency of subject with the homozygote of 12 repeat allele was significantly higher in patients with hypertension compared with control subjects (987 cases, 924 controls) (P=0.030; odds ratio=1.24) at a novel VNTR polymorphism of CIAS1 intron 4 loci. We also found that the mean of systolic blood pressure of homozygotes of 12 repeat allele was 6.4 mmHg higher than those of homozygotes of non-12 repeat allele in male random population (P=0.009). The frequency of six SNPs spanning of the CIAS1 gene was not significantly between patients and controls. The real-time PCR analysis showed that among healthy young adults, 12-12 subjects expressed CIAS1 mRNA in peripheral leukocytes significantly more abundantly than homozygote of non-12 repeat alleles subjects (P<0.05). Reporter gene assay of the CIAS1-VNTR in HL60 stimulated by lipopolysaccharides showed that the intronic sequence involving 12 repeat increased the expression of luciferase compared with 9, 7, and 6 repeats. Thus, we propose here the CIAS1 is associated with EH through the dominant expression of transcripts, which may depend on the CIAS1-VNTR genotype.

Alleles↗

PubMed2006

Mutation of the follicle-stimulating hormone receptor gene 5'-untranslated region associated with female hypertension.

Inactivating mutations in the follicle-stimulating hormone receptor (FSHR) gene have been reported to cause hereditary hypergonadotropic ovarian failure. It has been found recently that the FSHR knockout mouse exhibits hypertension. The aim of the present study was to investigate the association between polymorphisms in the human FSHR gene and essential hypertension (EH) by using single nucleotide polymorphisms (SNPs). We selected 5 SNPs in the gene (rs1394205, rs2055571, rs11692782, rs1007541, and rs2268361) and performed 2 genetic case-control studies in different populations. A confirmative case-control study was performed using 1035 EH patients and 1058 age-matched controls. Transcriptional activities were measured with a luciferase assay system. The first case-control study found that the A allele of rs1394205 was significantly higher in EH females (P=0.010). In addition, in the confirmative case-control study, there was a significant difference for this SNP between female normotensive subjects (44.5%) and EH patients (50.7%) (P=0.043). Multiple logistic regression analysis in female subjects also revealed a significant association of subjects with the A allele of rs1394205 with EH (P=0.033), with the odds ratio calculated as 1.68 (95% CI: 1.04 to 2.73). Transcriptional activity of the A allele was 56+/-8% (mean+/-SD) of that observed for the G-type allele (P=0.001). Serum estradiol levels were significantly lower in patients with the A/A genotype than in patients without the A/A genotype (P=0.004). The SNP in the 5'-untranslated region of the FSHR gene affects levels of transcriptional activity and is a susceptibility mutation of EH in women.

5' Untranslated Regions↗

PubMed2006

Interaction between serotonin 2A receptor and endothelin-1 variants in association with hypertension in Japanese.

Serotonin has been implicated in the pathogenesis of hypertension because of its ability to induce vasoconstriction via stimulation of serotonin 2 (5-HT2) receptors. Recently, an association between the T102C functional polymorphism of the serotonin 2A (5-HT2A) receptor gene and hypertension in the UK has been reported. Another association study, however, failed to replicate this association in a Chinese population. We therefore investigated the possible association between the 5-HT2A T102C polymorphism and hypertension in two large Japanese populations (n = 2,968 total). We also investigated the possible interaction between the 5-HT2A T102C polymorphism and the G/T (Lys198Asn) polymorphism of the endothelin-1 (ET-1) gene, based on robust biological evidence for the existence of an interaction between the serotonin and endothelin systems. The results showed that there was no significant difference in the frequencies of the alleles and genotypes between the hypertensive and normotensive subjects. However, a significant interaction between the 5-HT2A T102C and ET-1 G/T polymorphisms in their association with hypertension (p = 0.0040) and with diastolic blood pressure (p = 0.0013) was revealed. A marginally significant interaction in the association with systolic blood pressure was also shown (p = 0.045). The associations of the 5-HT2A T102C polymorphism with hypertension and diastolic blood pressure in ET-1 T allele carriers were significant (p = 0.0056 and 0.021, respectively). The association of the 5-HT2A T102C polymorphism with systolic blood pressure in ET-1 T allele carriers was marginally significant (p = 0.054). Thus, the present study suggests that the 5-HT2A T102C and ET-1 G/T polymorphisms are interactively associated with hypertension.

Adult↗

PubMed2006

[Angiotensin-converting enzyme gene polymorphism].

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Aging↗

PubMed2005

Resistin SNP-420 determines its monocyte mRNA and serum levels inducing type 2 diabetes.

Resistin, secreted from adipocytes, causes insulin resistance in rodents. Its roles and main source in humans remain unknown. The G/G genotype of resistin single nucleotide polymorphism, SNP-420, induces type 2 diabetes mellitus (T2DM) by increasing promoter activity. We elucidated factors correlated with serum resistin and effects of SNP-420 on monocyte resistin mRNA. In 198 T2DM and 157 controls, fasting serum resistin was higher in T2DM. Multiple regression analysis revealed that SNP-420 genotype was the strongest determinant of serum resistin. In T2DM, 1-year duration of T2DM and 1% HbA1c was also correlated with 0.19 and 0.54 ng/ml serum resistin, respectively. Logistic regression analysis revealed that serum resistin was an independent factor for T2DM. In 23 healthy volunteers, monocyte resistin mRNA was positively correlated with its simultaneous serum levels and was higher in G/G genotype. Thus, SNP-420 determines monocyte mRNA and serum levels of resistin, which could induce T2DM.

Adipocytes↗

PubMed2005

Radial augmentation index: a useful and easily obtainable parameter for vascular aging.

BACKGROUND: It has been shown that the systolic augmentation index (AI) in the central arteries, including the aorta and carotid arteries, changes with age. The AI can also be obtained from the peripheral arteries. The possible usefulness of AI obtained from the radial artery as an index for vascular aging was investigated. METHODS: Radial arterial waveforms were obtained from 632 subjects with no cardiovascular disease, using radial tonometry. Radial AI was calculated as follows: (Second peak systolic blood pressure [SBP2] - diastolic blood pressure [DBP]) / (first peak SBP - DBP) x100 (%). RESULTS: Radial AI was significantly higher in women than in men (81.1% +/- 16.1% compared with 69.5% +/- 16.3%, P < .001). Radial AI was positively related to age in healthy men and women (r = 0.619, P < .001, and r = 0.644, P < .001, respectively). When comparing subjects in their 20s to those in their 70s, radial AI increased 1.56 times (from 53.2% to 83.0%) in men and 1.49 times (from 64.6% to 96.4%) in women. Multiple regression analysis showed that age is a potent predictor of radial AI in addition to gender, DBP and pulse rate. CONCLUSIONS: These findings indicate that simple and easily-obtainable radial AI is age-dependent and could be a useful index of vascular aging.

Aging↗

PubMed2005

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms.

A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.

Adolescent↗

PubMed2005

Classic Rett syndrome in a boy with R133C mutation of MECP2.

About 80% of female patients with Rett syndrome (RTT) display a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, but most males with MECP2 mutation experience severe fatal encephalopathy or non-specific X-linked mental retardation (XLMR). The existence of male RTT has been extensively discussed. We report herein a boy with classic RTT in a family with a missense mutation in MECP2. The mother exhibited slight mental retardation and was a carrier for R133C. The patient could stand with support at 12-months-old, and stereotypic hand movements appeared at 3-years-old. He became bed-ridden by 8-years-old. The R133C mutation was present in MECP2 without somatic mosaicism. A sister with R133C displayed classic RTT. The R133C mutation has been detected in female patients with classic and preserved speech variant RTT, but not in males with non-specific XLMR. These results suggest that clinical phenotypes caused by DNA mutation in MECP2 are determined by position of the mutation in the gene, and R133 represents a critical amino acid residue in the induction of RTT symptoms in humans.

Child↗

PubMed2005

Delayed reflection pressure wave: new aspects for postprandial hypotension.

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Adult↗

PubMed2005

Association of dopamine beta-hydroxylase polymorphism with hypertension through interaction with fasting plasma glucose in Japanese.

Dopamine-beta-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine and is released from sympathetic neurons into the circulation. Several lines of evidence, including the finding of elevated plasma DBH activity in essential hypertension, suggest an important role of DBH in hypertension. Recently, a novel polymorphism (-1021C/T) in the 5' flanking region of the DBH gene has been shown to account for 35-52% of the variation in plasma DBH activity. We therefore investigated the possible association between the DBH -1021C/T polymorphism and hypertension in a large Japanese population. Moreover, because the development of hypertension is considered to be due at least partly to gene-environmental interactions, we also investigated the possible interactions between the DBH -1021C/T polymorphism and environmental factors. Consequently, we found a significant interaction between the DBH -1021C/T polymorphism and fasting plasma glucose (FPG) in the association with hypertension. CC homozygotes showed a steeper increase in probability of hypertension with FPG than T allele carriers. We also found a marginally significant trend suggesting the presence of an interaction between the DBH -1021C/T polymorphism and FPG in the association with blood pressure. Consistent with the presence of the interaction, we found that a 19 bp sequence containing the DBH -1021C/T polymorphism includes two palindromic non-canonical E boxes separated by 5 bps, and closely resembles the glucose response element of the L-type pyruvate kinase gene. These findings could be helpful in conducting further molecular and biological studies on the relationship among glucose metabolism, the sympathetic nervous system, and hypertension.

Aged↗

PubMed2005

Orthostatic systolic hypotension and the reflection pressure wave.

Orthostatic hypotension (OH) is a potent predictor of cardiovascular frailty. Although OH is determined by changes in brachial blood pressure (BP), it has been reported that there are significant differences between central BP and peripheral BP. The prevalence of OH has been reported to be higher in subjects with isolated systolic hypertension. Since an early returning of the reflection pressure wave due to advanced arterial stiffness is one of the underlying mechanisms of systolic hypertension, a significant association between alterations of the reflection pressure wave and OH has been hypothesized. To explore this hypothesis, the orthostatic changes in carotid BP and arterial waveform were evaluated. The study subjects were 155 community residents (69 +/- 7 years old). Carotid and brachial BP were measured simultaneously in the supine position and 1 min after standing using a cuff-oscillometric and tonometric method. The carotid augmentation index (AIx) was obtained from the pressure waveform. The orthostatic decline of BP was more prominent in the carotid artery than the brachial artery. Nine subjects were diagnosed with orthostatic systolic hypotension (OSH) from brachial BP, while 21 subjects were diagnosed from carotid BP (p < 0.001). The orthostatic change in carotid systolic BP was significantly associated with that in carotid AIx (r = 0.361, p < 0.001). The decline of the reflection component of carotid pulse pressure (-4.0 +/- 8.4 mmHg) was more prominent than that of the incident component (-1.2 +/- 9.9 mmHg, p = 0.002). These results indicate that evaluation of brachial BP may not represent the orthostatic changes in central BP. Alteration of the reflection pressure wave could be one of the underlying mechanisms of OSH in the central artery.

Aged↗

PubMed2005

Combined analysis of polymorphisms in angiotensinogen and adducin genes and their effects on hypertension in a Japanese sample: The Shigaraki Study.

We examined the interactions between lifestyle and polymorphisms of salt-sensitive genes and their effects on hypertension in a general Japanese sample (The Shigaraki Study). The study group consisted of 2,902 subjects who underwent a medical examination in 1999 in Shigaraki, a suburban area in Shiga. Among 1,647 subjects not receiving antihypertensive medication, in a combined analysis of angiotensinogen (AGT) and adducin (ADD1) polymorphisms, double homozygosity of 235Thr or 460Trp was not found to be associated with hypertension. A multiple logistic regression analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [95% CI]: 1.06-1.08), body mass index (BMI) (OR: 1.18, 95% CI: 1.13-1.23), alcohol consumption (OR: 1.39, 95% CI: 1.16-1.66), family history of hypertension (OR: 1.57, 95% CI: 1.18-2.07), and combined AGT M235T Thr/Thr and ADD1 Trp/Trp polymorphisms (OR: 1.37, 95% CI: 1.03-1.82) were associated with hypertension. However, there was no interaction between eating salty food and combined AGT and ADD1 polymorphisms. Furthermore, eating salty food was not associated with hypertension in a multivariate analysis. Therefore, a combination of the AGT and ADD1 polymorphisms appears to be associated with hypertension. However, a simple questionnaire regarding salt intake was not sufficient to confirm the relationship between salt intake and hypertension and/or salt-sensitive genes.

Adult↗

PubMed2005

Hypotension associated with prone body position: a possible overlooked postural hypotension.

Conditions related to the dysregulation of blood pressure (BP), such as orthostatic hypotension, have been shown to be significantly associated with cardiovascular disease. Recently, the prone body position has been recognized as a possible postural factor leading to BP dysregulation. We conducted a cross-sectional study to investigate the BP response to a change in body position from supine to prone. The study subjects consisted of 271 middle-aged healthy males, randomly selected from the employees of a large manufacturing enterprise in Ehime Prefecture, Japan. Brachial BP and heart rate were measured in a sitting, supine and prone position, in that order, and each difference was defined as a postural change. The postural changes in aortic hemodynamics were also assessed using a SphygmoCor system. The basal BP measured in the sitting position was significantly decreased in the supine position (132+/-18 to 130+/-17 mmHg, p<0.001). A further reduction was observed after the postural change from supine to prone (130+/-17 to 125+/-16 mmHg, p<0.001). The heart rate was increased with the supine-to-prone postural change (4.1+/-5.8 beats/min, p<0.001), while it showed a significant decrease with the sitting-to-supine postural change (-7.6+/-5.6 beats/ min, p<0.05). The impact of BP reduction was more prominent in the aortic artery (-3.3+/-6.7%) than the brachial artery (-3.0+/-6.3%, p=0.020). Multiple regression analysis showed that basal systolic BP was a solely significant determinant of the prone-hypotension (beta=-0.309, p<0.001). In conclusion, these results indicate that lying in a prone posture could lead to unregulated postural hypotension, which has the possibility of being a novel predictor of cardiovascular frailty.

Adult↗

PubMed2004

Association of GNB3 gene with pulse pressure and clustering of risk factors for cardiovascular disease in Japanese.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) mediate many pathways including the beta-adrenergic signaling pathway. The C825T polymorphism in the gene coding for the beta3 subunit of G proteins (GNB3) has been shown to be associated with several phenotypes such as hypertension, obesity, and diabetes mellitus comprising the metabolic syndrome. The GNB3 C825T polymorphism may therefore be associated with many atherosclerosis-related phenotypes. On these grounds, we studied the C825T polymorphism in relation to atherosclerosis-related phenotypes in a large Japanese population. Analyses in general linear models showed that T carriers had a significantly wider pulse pressure (P=0.0089) as well as a significantly higher systolic blood pressure (P=0.026). In contrast, analyses in logistic regression models showed that the C825T polymorphism was not significantly associated with each of the four major classical risk factors for cardiovascular and cerebrovascular disease (obesity, hypertension, hypertriglyceridemia, and diabetes mellitus). However, a significantly higher percentage of subjects had none of the four disorders in CC homozygotes than in T carriers (P=0.026). Thus, the C825T polymorphism was significantly associated with clustering of these four risk factors. Although the effect of the gene on each phenotype appears to be weak, considering the combined impact of the effects of the C825T polymorphism on risk factors, the GNB3 gene may be an important gene for human health.

Arteriosclerosis↗