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T Katsuya

Publications and source records attributed to T Katsuya.

At least 37 records · Page 2Linked to original sources
PubMed2000

Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension.

Even if the importance of angiotensinogen (AGT) gene has been known in gene targeting animals and humans genetic studies, its precise mechanism and the interaction among AGT gene variants, plasma AGT concentration and risk for hypertension remain uncertain. We examined whether AGT gene variants predispose to hypertension via an increase of plasma AGT concentration. Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RIA. Using 9 AGT gene variants which included new polymorphisms (G-152A and T+31C), we examined the association with hypertension and with plasma concentration by a case-control study. Haplotype analysis revealed that G-6A, T+31C and M235T polymorphisms were in absolute linkage disequilibrium and were associated with hypertension but not with plasma AGT level. On the other hand, -1074t;T235 haplotype was associated with an increase of AGT level but not with hypertension. In the haplotype analysis, only H3 haplotype frequency, which contained G-6, T+31 and M235 alleles, was significantly increased in normotensive subjects, suggesting that this haplotype is associated with a hypotensive effect. According to combined haplotype analysis of diallele and microsatellite markers, it remains a possibility that M235T, T+31C, G-6A, A-20C and G-1074T polymorphisms may play an important role in increased risk for essential hypertension. Our results suggest that the positive association between AGT polymorphism and hypertension is not simply explained by an increase of plasma AGT concentration.

Alleles↗
PubMed2000

Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men : the Suita Study.

BACKGROUND: The Framingham Study recently revealed that the homozygous deletion polymorphism of the angiotensin-converting enzyme gene (ACE DD) is associated with increased risk for essential hypertension in a male-specific manner. However, this association has not been confirmed in races other than whites. METHODS AND RESULTS: Using a large number of Japanese subjects (n=5014) that were randomly selected from the general population (the Suita Study), we examined the association between ACE DD and hypertension. The frequency of DD (17.1%) in hypertensive men was significantly higher (P<0.0015) than that (11.8%) in other mildly hypertensive or normotensive men, and the estimated odds prevalence for hypertension (DD vs II) was 1.75 (95% CI 1.21 to 2.53). In contrast, no significant association was confirmed in women (OR 1.17, 95% CI 0.79 to 1.72). CONCLUSIONS: Despite the lower frequency of the DD genotype in Japanese than in whites, the ACE gene polymorphism was associated with increased risk for hypertension, suggesting that this polymorphism is a mild but certain genetic risk factor for essential hypertension in men.

Age Factors↗
PubMed2000

Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure.

The activity of a sodium-proton exchanger is enhanced in the patients with essential hypertension and regulated via G-protein, which is a signal transducer between receptors and intracellular effectors. A recent study has revealed that a novel variant (C825T) in exon 10 of the gene encoding the beta3 subunit of heterotrimetric G proteins (GNB3) is a genetic factor predisposing to hypertension in Caucasians. We examined the association between GNB3/ C825T and blood pressure, lipids, electrolytes, and other parameters in a Japanese population. Subjects (n = 352) were selected from the Ohasama Study, the population of which is regarded as from a rural community in Japan. To obtain precise clinical measurements, 24-h ambulatory blood pressure monitoring (ABPM), brain magnetic resonance imaging (MRI), and carotid ultrasonography (CUS) were conducted in this population. In addition, we recruited 762 subjects from outpatients at the Osaka University Medical School to carry out the association study between hypertension and GNB3. The GNB3 genotype distribution did not differ significantly between normotensives and hypertensives in either of the two studies. The T825 allele of GNB3 was not associated with the presence of hypertension, blood pressure level, the number of brain lacunae or carotid wall thickness. However, the serum potassium and total cholesterol levels were significantly higher in subjects with the T allele (P < .005). The T825 allele of GNB3 is associated with increased serum potassium and total cholesterol levels but not with blood pressure in a Japanese population.

Adult↗
PubMed2000

Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction. The Ohasama study.

The polymorphism of the angiotensin-converting enzyme gene is considered to be associated with increased risk for stroke, but there is a diversity in the results obtained. The genetic involvement of the renin-angiotensin system in stroke also remains unclear. To predict the genetic risk of lacunar infarction, we conducted an association study in an Ohasama population, which is the cohort in a rural region of northern Japan. A total of 134 subjects without major neurological, cardiovascular, or metabolic disorders were recruited. Using brain magnetic resonance imaging, the number of lacunae in each of four brain regions were calculated, and periventricular hyperintensity was classified into five grades. We used the following four candidate gene polymorphisms: angiotensin converting enzyme (ACE)/Insertion(I)-Deletion(D), angiotensinogen (AGT)/M235T, angiotensin II type 1 receptor (AT1)/ A1166C, type 2 receptor (AT2)/C3123A, to examine the association between polymorphisms and the severity of lacunar infarction. AGT/M235T was significantly associated with the number of lacunae in the brain stem, the basal ganglia (P < .05), and whole brain (P < .005) regions. The AT1 polymorphism was also significantly associated with the number of lacunae in the basal ganglia and whole brain regions (P < .05), and with periventricular hyperintensity grade (P < .005) in the younger population. However, ACE and AT2 polymorphisms failed to show an association with either the number of lacunae or the PVH grade. We concluded that AGT and AT1 polymorphisms are independent genetic risk factors for lacunar infarction.

Aged↗
PubMed2000

Deletion polymorphism of angiotensin-converting enzyme gene is associated with postprandial hyperglycaemia in individuals undergoing general check-up.

1. Deletion polymorphism, DD, of the angiotensin-converting enzyme (ACE) gene is reported to be related to cardiovascular disease, which is frequently based on insulin resistance. 2. To clarify the relationship between the ACE genotype DD and plasma glucose increases after an oral glucose load, we performed 75 g oral glucose tolerance test (OGTT) in 301 nondiabetic men (age range 30-60 years) undergoing general check-up. 3. Insertion/deletion (I/D) polymorphism of the ACE gene was explored using a polymerase chain reaction. The frequency of the II, ID and DD genotypes was 0.43, 0.43 and 0.14, respectively. 4. There were no differences in baseline clinical characteristics between subjects with each ACE genotype. 5. The mean (+/- SEM) plasma glucose level at 60 min of the OGTT was significantly higher in subjects with the DD genotype (170.8 +/- 6.9 mg/dL) than in subjects with either the II or ID genotype (mean value for two groups 156.6 +/- 2.7 mg/dL; P < 0.05). Moreover, the mean percentage change of plasma glucose after 60 min of the OGTT, a marker of plasma glucose increase, was significantly higher in individuals with the DD genotype than in individuals with either the II or ID genotypes. 6. In contrast, the mean fasting plasma glucose level, the plasma glucose level at 120 min, the glucose response area and the fasting insulin level were not different between individuals with the DD genotype and individuals with other genotypes. 7. In conclusion, subjects with the DD genotype showed transiently higher levels of plasma glucose after an oral glucose load than subjects with other genotypes. Further studies are required to determine whether the association between ACE genotype and postprandial hyperglycaemia influences the incidence of cardiovascular disease and diabetes mellitus.

Adult↗
PubMed2000

Japanese individuals do not harbor the T594M mutation but do have the P592S mutation in the C-terminus of the beta-subunit of the epithelial sodium channel: the Ohasama study.

OBJECTIVE: To assess the implications of polymorphisms of the amiloride-sensitive epithelial sodium channel in essential hypertension in the Japanese population by determining the incidence of the T594M mutation in the , subunit of the epithelial sodium channel, and by screening the C-terminus of the epithelial sodium channel. METHODS: Single-strand confirmational polymorphism (SSCP) analysis using two sets of primers which cover the last two-thirds of the last exon coding the B epithelial sodium channel and modification of a specific enzyme restriction site (NlaIII) for the T594M mutation were performed on 803 Japanese subjects. They were randomly selected from the study participants representative of a general population of Ohasama, Japan, who measured their home blood pressure. Polymerase chain reaction (PCR) products presenting a shift in SSCP gel, as well as controls, were directly sequenced by autoanalyser to identify the mutation. RESULTS: SSCP analysis identified altered migration in five subjects. Four SSCP variants found by sequencing were heterogeneous for the P592S (CCT to TCT) mutation conserving the PY motif, although it was not significantly associated with either home or casual blood pressure values. The resting polymorphism was at codon Thr 594, leading to no change in the amino acid sequence (ACG to ACA). None of the PCR products were modified by NlaIII, indicating the absence of the T594M mutation. CONCLUSIONS: The epithelial sodium channel variants at the C-terminus are not involved in the common form of essential hypertension in Japanese.

Adult↗
PubMed2000

Genetic analysis of essential hypertension in Japanese populations.

The reverse genetic approach, which examines genetic factors underlying the root of pathogenesis first, is a powerful tool to clarify the genetic cause of essential hypertension. Using the rat cross model, studies of the genetically hypertensive inbred rat model indicated several candidate loci on the rat chromosome responsible for blood pressure, but failed to identify the exact causal gene. Moreover, it was not certain that the rat data really reflect the human case. Thus, we shifted our focus to human genetics and carried out case control studies using the candidate gene approach. We mainly focused on gene components of the renin-angiotensin system as candidates, finding that angiotensinogen gene polymorphisms are genetic predisposing factors for hypertension. However, the results obtained from case-control studies using Japanese subjects were not consistent, suggesting that there was a problem in control sampling. In our recent study, we recruited more than 5,000 residents of an urban community as a general population and examined the association between genetic factors and their health status. Our results indicate that angiotensin-converting enzyme gene polymorphism is a male-specific genetic risk for essential hypertension. In light of our previous investigations, we present a discussion concerning the design of future studies of the genetics of hypertension.

Angiotensinogen↗
PubMed2000

Association of polymorphism in the promoter region of the apolipoprotein E gene with diastolic blood pressure in normotensive Japanese.

The epsilon4 allele of apolipoprotein E (APOE) is reported to be a genetic risk factor of atherosclerosis through hyperlipidemia and late-onset Alzheimer's dementia. A recent report showed that a genetic variant (A -491T) in the promoter region of the APOE gene increases the risk of Alzheimer's disease. In the present study, we examined whether these APOE polymorphisms were genetically involved in essential hypertension. Japanese hypertensives (n=180) with a family history of hypertension and normotensive controls (n=195, sex and age matched with hypertensives) were recruited from the outpatients of Osaka University Hospital, and an informed consent to participate in the study was obtained from each person. APOE polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the A -491 allele in hypertensives and normotensives were 0.98 and 0.97, respectively, and the TT/-491 genotype was not found in either group. No significant differences between hypertensives and normotensives were observed in allele frequencies in either APOE polymorphism; however, the mean diastolic blood pressure in normotensive subjects with AA/-491 was significantly higher than in the subjects with AT/-491 (p < 0.01). These results suggest that the presence of the APOE promoter polymorphism is not a major risk factor for hypertension but that it does have some minor effect on basal blood pressure variation.

Adult↗
PubMed1999

Human prostacyclin synthase gene and hypertension : the Suita Study.

BACKGROUND: Prostacyclin (prostaglandin I(2)) is a strong vasodilator that inhibits the growth of vascular smooth muscle cells and is also the most potent endogenous inhibitor of platelet aggregation. Therefore, it has been considered to play an important roles in cardiovascular disease. On the basis of the hypothesis that variations of the prostacyclin synthase gene may also play an important role in human cardiovascular disease, we performed a screening for variations in the human prostacyclin synthase gene. METHODS AND RESULTS: We have detected a repeat polymorphism in the promoter region of the human prostacyclin synthase gene. The number of 9-bp (CCGCCAGCC) repeats in the promoter region, which encodes a tandem repeat of Sp1 transcriptional binding sites, varied between 3 and 7 in Japanese subjects. Luciferase reporter analysis indicated that the alleles of 3 and 4 repeats (R3 and R4, respectively) had less promoter activity in cultured human umbilical vein endothelial cells. We then investigated the possible association of this repeat polymorphism with blood pressure in a large population-based sample (the Suita Study), which consisted of 4971 Japanese participants. Multivariate models indicated that participants with the R3R3, R3R4, or R4R4 genotype (SS genotype, n=80) had significantly higher systolic pressure (P=0.0133) and pulse pressure (P=0.0005). The odds ratio of hypertension (140/90 mm Hg) for the SS genotype was 1.942 (95% confidence interval 3.20 to 1.19, P=0.0084). CONCLUSIONS: Repeat polymorphism of the human prostacyclin synthase gene seems to be a risk factor for higher pulse pressure and is consequently a risk factor for systolic hypertension in the Japanese population.

Adult↗
PubMed1999

Pharmacogenetic analysis of the effect of angiotensin-converting enzyme inhibitor on restenosis after percutaneous transluminal coronary angioplasty.

Angiotensin-converting enzyme (ACE) inhibitors are reported to prevent neointimal formation after balloon injury in animal models, but in most prospective studies in humans, ACE inhibitors failed to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). The ACE genotype assigned by an insertion/deletion (I/D) polymorphism is known to affect the potency of ACE inhibitors in several renal diseases. The authors attempted to clarify whether the effect of ACE inhibitors on restenosis might be modified by the ACE genotype. A total of 126 patients was randomly and prospectively assigned to the control group and the imidapril group. In the imidapril group, patients received 5 mg imidapril daily, starting 1 day before PTCA and continuing for 3 to 6 months. Forty-six control (65 vessels) and 32 imidapril patients (43 vessels) completed the study. The minimal lumen diameter before and after the procedure did not differ significantly among the groups with the three genotypes (II, ID, and DD) in both the control and imidapril groups. Late luminal loss during the follow-up period was not related to the ACE genotype in the control group but was significantly related in the imidapril group (II, 0.63+/- 0.19 mm; ID + DD, 1.12+/-0.14 mm, p<0.05). Furthermore, in the II genotype, imidapril significantly reduced late loss and restenosis rate as defined by most of the frequently used definitions. In conclusion the ACE I/D polymorphism may influence the effect of ACE inhibitors in preventing restenosis after PTCA.

Aged↗
PubMed1999

[Genetic analysis of candidate gene polymorphisms in elderly hypertension].

Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (< 60) and elderly (> or = 60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging.

Aged↗
PubMed1999

[Gene loci and polymorphisms of angiotensin II receptor].

The gene encoding angiotensin II type 1 receptor (AT1) is mapped on 3q21-q25 region, and a polymorphism, A1166C, is located at 3'untranslated region (UTR). A1166C is associated with increased risk for hypertension, aortic stiffness, left ventricular hypertrophy and diabetic nephropathy, and synergistically increases the risk for ischemic heart disease with DD polymorphism of angiotensin converting enzyme gene. However, these results were still in controversy. On the other hand, the gene encoding angiotensin II type 2 receptor (AT2) gene is mapped on Xq22-q23 region, and a polymorphism, C3123A, is identified at 3'UTR of AT2 gene. However, any significant association with C3123A has not been obtained in case control studies yet.

Cardiomegaly↗
PubMed1998

A novel vascular modulator, hepatocyte growth factor (HGF), as a potential index of the severity of hypertension.

HGF (hepatocyte growth factor), a member of endothelium-specific growth factors, might contribute to protection and/or repair of vascular endothelial cells injured by high blood pressure (BP). If so, serum HGF level might be elevated in response to endothelial cell damage. To test this hypothesis, we measured serum levels of HGF in hypertensive and normotensive patients. Serum HGF concentration in hypertensive patients without any complication was significantly higher than normal subjects (p < 0.001). Serum HGF concentration showed a significant positive correlation with BP (p < 0.01). Interestingly, serum HGF concentration in hypertensive patients with complications was significantly higher than that in hypertensive patients without complication and normotensive subjects (p < 0.01). Of importance, hypertensive patients treated with antihypertensive drugs showed the same level of serum HGF concentration as normotensive subjects (p < 0.001). The present study demonstrated that serum concentration of HGF is significantly elevated dependent on the severity of hypertension, suggesting that HGF may be a new index of the severity of hypertension.

Antihypertensive Agents↗
PubMed1998

Angiotensin II type 1 receptor gene polymorphism is associated with increase of left ventricular mass but not with hypertension.

A genetic epidemiologic approach is useful to elucidate the genes responsible for hypertension. Genetic analyses of the components of the renin-angiotensin system have succeeded in showing an association between their polymorphism and hypertension. Recently, two types of angiotensin II receptor were cloned and characterized. To examine the genetic contribution of angiotensin II type 1 receptor (AT1) and type 2 receptor (AT2) genes in human essential hypertension, a case-control study was performed in Japanese subjects. The study comprised 321 subjects with hypertension who satisfied the criteria for essential hypertension, together with 215 age and sex matched controls. The significance of the differences in genotype distribution between hypertensive and normotensive subjects was examined by chi2 analysis. Neither AT1 nor AT2 gene variants were associated with human essential hypertension in the Japanese subjects. However, the AT1 receptor gene polymorphism was associated with left ventricular mass index in normotensive subjects. The study results suggest that gene polymorphisms of both angiotensin II receptors are not directly involved in the increase of genetic risk for hypertension, but that the AT1 receptor gene might contribute genetically to the increase of left ventricular mass.

Aged↗