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Tetsuro Miki

Publications and source records attributed to Tetsuro Miki.

66 records · Page 4Linked to original sources
PubMed2002

Molecular evidence of presenilin 1 mutation in familial early onset dementia.

Early onset familial Alzheimer disease (FAD) has been associated with mutations in three genes, of which presenilin 1 (PSEN1) mutations are the most frequent. We reported previously a variant form of FAD, due to deletion of exon 9 of PSEN1, with spastic paralysis and rigidity. We describe a novel PSEN1 mutation in a family of Japanese origin with six affected individuals of both genders in two generations. The disease is characterized by presenile dementia, which is preceded by spastic paraparesis and apraxia. This mutation, which is predicted to cause a missense substitution of serine for glycine, occurred at codon 266 in exon 8 of PSEN1. The mutation was not found in 200 controls and 200 sporadic AD patients. On this basis alone, it seems this mutation is pathogenic. Our findings provide a new clue to the etiology of the familial early onset dementia.

Adult↗
PubMed2002

Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy.

Atrial fibrillation (AF) occurs in about 20% of patients with hypertrophic cardiomyopathy (HCM). HCM patients with AF have an increased risk for clinical decline and thromboembolism. In addition, AF is known to be associated with the atrial renin-angiotensin system (RAS). However, the relation between AF and the RAS in HCM has not been investigated. We genotyped the insertion/ deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in 138 HCM patients (26 with AF, 112 with sinus rhythm). Distribution of the ACE genotypes (DD, ID, and II) among the total HCM patients was 15%, 46%, and 38%. AF was documented in 3 patients with the DD genotype, 7 with the ID genotype, and 16 with the II genotype (P < 0.03 vs. sinus rhythm group). The odds of AF were 3.2-fold greater in patients with the II genotype than in those with the other genotypes (P = 0.009, 95% confidence interval = 1.3-7.8). Kaplan-Meier curves examining the time to the first documented AF event showed a significant difference between genotypes during the follow-up period (mean 116 months, P < 0.05). These findings suggest that the II genotype of the ACE gene is a significant risk factor for AF in patients with HCM.

Aged↗
PubMed2002

Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension.

OBJECTIVE: The genetic background of orthostatic hypotension, an important risk factor for future cardiovascular morbidity and mortality, was investigated. DESIGN AND METHODS: The study subjects comprised 415 community-dwelling individuals, who were free from any cardiovascular complications, aged 50 years or older (mean age 70.5 +/- 9 years). Basal systolic blood pressure (SBP) was measured twice in supine posture after resting for more than 10 min. The orthostatic change in SBP was determined at 1 min and 3 min after standing up. The maximum change in SBP after standing was determined. Orthostatic hypotension was defined as a decline in SBP greater than 20 mmHg. The polymorphisms of genes encoding components of the renin-angiotensin system and sympathetic nervous system, which play pivotal roles in postural change in blood pressure regulation, were determined. RESULTS: There were no significant associations between the maximum change in SBP, the prevalence of orthostatic hypotension and gene polymorphisms of angiotensin-converting enzyme I/D, angiotensinogen M235T and angiotensin II type 1 receptor A1166C. On the contrary, polymorphism of the Gs protein alpha-subunit (GNAS1) T131C was significantly associated with the maximum change in SBP after standing [1.9 +/- 16 versus -3.6 +/- 16 mmHg (TT + TC versus CC), P = 0.008]. The prevalence of orthostatic hypotension was significantly different among GNAS1 genotypes (chi squared = 10.12, P = 0.011) and G-protein beta 3 subunit (GNB3) genotypes (chi squared = 6.12, P = 0.020). Multiple logistic regression analysis showed that both GNAS1 CC genotype [odds ratio (OR) = 2.79, 95% confidence interval (CI) 1.35-5.79, P = 0.006] and GNB3 C allele (OR = 1.78, 95% CI 1.06-3.00, P = 0.030) were independent risks for orthostatic hypotension. CONCLUSIONS: These findings indicate that genes encoding sympathetic nervous components could be involved in the predisposition for orthostatic hypotension.

Aged↗
PubMed2002

Association of GNAS1 gene variant with hypertension depending on smoking status.

The beta-adrenoceptor (beta-AR) G(s) protein system has been shown to have important roles in the cardiovascular system. The gene encoding the alpha-subunit of G(s) proteins (GNAS1) is a candidate genetic determinant for hypertension. We studied the GNAS1 T393C polymorphism in >2000 Japanese individuals. chi(2) test showed a marginally significant difference in the frequencies of the alleles (P=0.036) and genotypes (P=0.094) between hypertensives and normotensives. Because hypertension is considered to be a complex disorder resulting from interactions between genetic and environmental factors, we further analyzed the T393C polymorphism, with consideration of interactions between the polymorphism and confounding factors in regression models. These analyses showed a significant interaction between the polymorphism and cigarette smoking in the pathogenesis of hypertension (P=0.0005). The interaction was reflected in a significant association of the polymorphism with hypertension in nonheavy smokers (P=0.0028; odds ratio, 1.52; 95% confidence interval, 1.16 to 2.00). A significant interaction between the polymorphism and aging in the pathogenesis of hypertension was also shown in nonheavy smokers. These findings may be helpful in conducting further molecular and biological studies on the relationship among cigarette smoking, the beta-AR-G(s) protein system, and hypertension.

Age Factors↗
PubMed2002

Chlamydia pneumoniae seropositivity is associated with increased plasma levels of soluble cellular adhesion molecules in community-dwelling subjects: the Shimanami Health Promoting Program (J-SHIPP) study.

BACKGROUND AND PURPOSE: In vitro studies have demonstrated that Chlamydia pneumoniae infection of the endothelium increases the expression of adhesion molecules and chemokines, indicating that C pneumoniae infection affects the adhesion and recruitment of leukocytes to the endothelium, which is believed to be involved in the initial steps of atherosclerosis. However, whether chronic C pneumoniae infection increases these molecules in vivo has not been elucidated. METHODS: The association between C pneumoniae seropositivity and plasma concentrations of soluble adhesion molecules and a chemokine was investigated in 200 community-dwelling residents free from cardiovascular diseases and medication. Plasma levels of IgA and IgG antibodies to C pneumoniae were measured by enzyme-linked immunosorbent assay. Indices of IgG and IgA antibodies were determined as the ratio to the standardized positive control. The subjects were divided into 3 groups according to the indices of antibodies: C pneumoniae seronegative (n=57, IgA<1.0 and IgG<1.0), C pneumoniae intermediate (n=81, 1.0< or =IgA> or =1.1 or 1.0< or =IgG> or =1.1), and C pneumoniae seropositive (n=62, IgA>1.1 and IgG>1.1). Plasma concentrations of soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1, and monocyte chemoattractant protein-1 were determined by enzyme-linked immunosorbent assay. RESULTS: Plasma concentrations of ICAM-1 (392+/-118, 398+/-94, 470+/-154 ng/mL, P=0.0004) and vascular cellular adhesion molecule-1 (402+/-146, 419+/-130, 472+/-181 ng/mL, P=0.03) were significantly different among the C pneumoniae seronegative, intermediate, and seropositive groups respectively. However, plasma monocyte chemoattractant protein-1 was not significantly different among the 3 groups. Stepwise regression analysis showed that plasma concentration of ICAM-1 was significantly associated with C pneumoniae seropositivity, independent of other known risk factors for atherosclerosis and carotid intima-media thickness. CONCLUSION: These findings indicate that C pneumoniae seropositivity is associated with higher plasma concentrations of soluble forms of adhesion molecules in the general population. The increase in circulating adhesion molecules may underlie the mechanisms linking C pneumoniae infection and atherosclerosis in vivo.

Aged↗
PubMed2002

Genotype-specific association between circulating soluble cellular adhesion molecules and carotid intima-media thickness in community residents: J-SHIPP study. Shimanami Health Promoting Program.

Plasma levels of soluble forms of cellular adhesion molecules (CAMs) and their relationships with carotid intima-media thickness (IMT) were investigated in community residents. Plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA in 200 community residents in Japan. Carotid IMT showed a weak but significant positive correlation with the plasma levels of both sICAM-1 (r=0.175, p=0.013) and sVCAM-1 (r=0.19, p=0.0075). Gene polymorphisms of angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T, angiotensin II type 1 receptor (AT1R) A1166C and apolipoprotein E (apoE) were determined for each subject. The plasma level of sVCAM-1 tended to be lower in subjects with the ACE DD genotype than in those with the ACE ID and II genotypes (373+/-94, 421+/-133, 443+/-135 ng/ml, respectively, p=0.056). However, there were no genotype-specific differences in the plasma levels of soluble forms of CAMs for the other genes examined. In a separate analysis, the plasma level of sICAM-1 was significantly associated with carotid IMT in ACE D carriers (ID + DD) (r=0.28, p=0.002), AGT M carriers (MT + MM) (r=0.32, p=0.0045), and subjects with apoE4 (r=0.35, p=0.036). In contrast, the plasma level of sVCAM-1 showed significant positive correlations with carotid IMT in subjects with the ACE II genotype (r=0.33, p=0.0027) or AGT TT genotype (r= 0.22, p=0.015), and subjects with apoE E2/E3 or E3/E3 (r=0.16, p=0.043). Stepwise regression analysis showed that plasma sVCAM-1 was independently associated with carotid IMT in subjects with the ACE II genotype or apoE4 genotype. Similarly, the plasma level of sICAM-1 was independently associated with carotid IMT in AGT M carriers. These findings suggest that genetic background could be involved in the association between plasma CAMs and atherosclerosis.

Aged↗
PubMed2002

Plasma hepatocyte growth factor and the relationship between risk factors and carotid atherosclerosis.

Hepatocyte growth factor (HGF) has been shown to have a unique stimulating property on the endothelium as well as an anti-apoptotic action on the endothelium. Through these mechanisms, HGF has been shown to have an anti-atherogenic action in animal models. In atherosclerotic disorders, the circulating level of HGF has been shown to be increased to compensate for its decline in tissue. However, whether increased circulating HGF has any influence on the development of atherosclerosis has not been elucidated. In the present study, the association between plasma HGF concentration and the risk factor-carotid atherosclerosis relationship was evaluated. Three hundred and seventeen community-dwelling subjects participated in the study. The plasma concentration of HGF was determined by enzyme-linked immunosorbent assay (ELISA). The subjects were divided into two groups according to the plasma level of HGF: a low HGF group (n=199, plasma HGF < 150 pg/ml) and a high HGF group (n=118, plasma HGF > or = 150 pg/ml). Risk factors for atherosclerosis were evaluated in each subject. Carotid ultrasonography was performed to measure carotid arterial intima-media thickness (IMT) and the presence of plaque. The association between carotid IMT and risk factors was then evaluated in the two HGF groups. The regression lines between age and carotid IMT were significantly different between the low HGF and high HGF groups (F[1,313]=5.98, p=0.015). The regression lines between systolic blood pressure and carotid IMT were also significantly different between the two HGF groups (F[1,313]=5.17, p=0.024). A general linear model showed that the interaction between age and plasma level of HGF was significantly associated with carotid IMT, suggesting that the plasma level of HGF modifies the age-related increase in carotid IMT. In addition, clustering of risk factors was evaluated in subjects with carotid atherosclerosis. The number of total risk factors in carotid atherosclerosis subjects with high plasma HGF was significantly greater than that in those with low HGF, even though the two groups had a similar magnitude of carotid atherosclerosis. In conclusion, these findings indicate that risk factor-dependent augmentation of carotid atherosclerosis could be influenced by circulating HGF.

Aged↗
PubMed2002

An interaction between systolic blood pressure and angiotensin-converting enzyme gene polymorphism on carotid atherosclerosis.

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE activity, with the D allele being associated with higher ACE levels than the I allele. Thus, chronic exposure to high levels of circulating and tissue ACE may well predispose to vascular wall thickening and atherosclerosis. However, the effect of the ACE gene on carotid atherosclerosis remains controversial. We investigated the association between ACE gene I/D polymorphism and risk factor-dependent augmentation of carotid arterial remodeling in subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid artery with intima-media thickness (IMT) by ultrasonography in 184 patients (mean age +/- SD, 67 +/- 14 years old) and studied whether any risk factor-gene interactions were associated with carotid atherosclerosis. Out of the 184 subjects, 71 had the ACE II genotype, 87 the ID genotype and 26 the DD genotype. There was no significant difference in IMT among the three ACE genotypes. In total subjects, multiple regression analysis showed that age, total-cholesterol (T-C), and HDL-cholesterol (HDL-C) were significantly associated with IMT. However, the association between risk factors and IMT was genotype-specific. Systolic blood pressure (SBP) and HDL-C were significantly associated with IMT in ACE D carriers (DD+ID), but not in subjects with the ACE II genotype. Similarly, T-C was significantly associated with IMT only in subjects with the ACE II genotype. A general linear model of the interaction between the ACE genotype and the conventional risk factors showed that the SBP-ACE genotype interaction were significantly associated with IMT (F = 7.915; p = 0.005). This finding further supports the idea that analysis of risk factor-gene interaction could be a useful tool for deriving specific predictive information about the development of atherosclerosis.

Aged↗
PubMed2002

The 4,752 C/T polymorphism in the presenilin 1 gene increases the risk of Alzheimer's disease in apolipoprotein E4 carriers.

OBJECTIVE: We sought to establish an association between sporadic Alzheimer's disease (AD) and presenilin 1 (PSEN1) gene polymorphisms in the Japanese population. METHODS: A 5 kb fragment containing the putative promoter of the PSEN1 gene for randomly selected control subjects was subcloned into plasmid and sequenced to screen novel polymorphisms in this region. Patients and controls were genotyped for five polymorphic markers in the PSEN1 region. We then constructed haplotypes using the computer program HAPLO and compared the frequencies between cases and controls. SUBJECTS: A total of 189 AD cases (NINCDS-ADRDA criteria) and 240 controls were studied. RESULTS: We discovered a novel polymorphism with high heterozygosity on -4,752 of the PSEN1 promoter region. A significant association was observed between the -4,752 C/T polymorphism and late-onset AD. The odds ratio for AD associated with the CC vs non-CC genotype was 1.59 (95% CI = 1.01-2.51), while that of epsilon 4 vs non-epsilon 4 in APOE gene was 4.41 (95% CI = 2.72-7.16). The C allele was associated with a further increase in the risk of AD in APOE epsilon 4 carriers. We found 12 major haplotypes using five polymorphisms. The distribution pattern was significantly different between cases and controls. CONCLUSION: The PSEN1 gene -4,752 C/T polymorphism modifies the risk for AD.

Alleles↗
PubMed2002

[Effect of elapsed time after standing up on orthostatic blood pressure change in the elderly].

The effect of time elapsed after standing on the orthostatic change in blood pressure was investigated. The study subjects were recruited from 237 community-dwelling elderly residents free from any history of cardiovascular disease and not on medication. Basal blood pressure was determined by averaging two determinations of supine blood pressure measured with an automatic oscillometric blood pressure recorder after resting for more than 10 minutes. Orthostatic change in systolic blood pressure (SBP) was determined as more than a 10% increase or decrease in SBP after standing. In the total population, maximum change in SBP was observed at 1 minute after standing-up. However, 8.4% and 7.2% of subjects showed abnormal increase or decrease in SBP only after 3 minutes. These results suggests that orthostatic dysregulation of blood pressure could be evaluated by measuring at 1 minute after standing up. However, if abnormal variation of blood pressure was not observed at 1 minute after standing up, repeated measurement at 3 minutes would be necessary.

Aged↗