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Biomedical subjects

Tetsuro Miki

Publications and source records attributed to Tetsuro Miki.

At least 19 recordsLinked to original sources
PubMed2006

Variations in the BDNF gene in autopsy-confirmed Alzheimer's disease and dementia with Lewy bodies in Japan.

BACKGROUND/AIM: Brain-derived neurotrophic factor (BDNF) is associated with the hippocampus and the nigrostriatal dopaminergic function. Data showing that its level was reduced in Alzheimer's disease (AD) and Parkinson's disease (PD) suggested that the BDNF function must play an important role in the pathogenetics of these diseases. Indeed, variation in the BDNF gene may confer susceptibility to AD and PD development. Recently, a functional BDNF Val66Met polymorphism has been found to be associated with episodic memory and hippocampal function, with intracellular trafficking, and with activity-dependent secretion of BDNF. To date, there have been several conflicting reports on the correlation between AD or PD and Val66Met or C270T polymorphism in the BDNF promoter region, although no data on this relationship have been published with respect to dementia with Lewy bodies (DLB). In the present study, we investigated a possible association between such BDNF polymorphisms and susceptibility to AD or DLB. METHODS: BDNF genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism method in autopsy-confirmed human samples. RESULTS AND CONCLUSION: On comparing patients and controls, the distribution of BDNF genotypes and alleles did not differ significantly. Our findings suggest that it is unlikely that these BDNF polymorphisms play a major role in the pathogenesis of AD and DLB in the Japanese population.

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

[An elderly fludrocortison-responsive woman with hyponatoremia].

An 89-years-old woman had anorexia for at least 1 month, and had been given symptomatic treatment at a nearby hospital. She was admitted to our hospital on August 22, 2003, for thorough examination and appropriate treatment for lack of spontaneity and appetite loss. On admission, laboratory data revealed hyponatremia (125 mEq/L) and hypoaldosteronism (0.7 ng/mL). Since hyponatremia did not improve by intravenous drip with saline, we identified the major cause of her complaint as hypoaldosteronism. She was treated with fludrocortisone (0.05 mg/day) and her condition improved immediately. Although she was discharged at that time, her condition shortly deteriorated. She was referred to our hospital on February 10, 2004 for medical treatment. On admission, inadequate oral intake, lack of spontaneity and weakness in her lower legs were noted. The plasma Na concentration was 127 mEq/L. Nasogastric tube feeding was started to prevent aspiration pneumonia because of her dysphagia. Fludrocortisone was given (0.2 mg/day), and she was able to swallow food without nasal feeding tube during the second month of therapy. Laboratory data including plasma natrium concentration were normal. Also she could perform bed-to-wheelchair transfer independently. This is a rare case of a critically ill elderly patient with hyponatremia caused by hypoaldosteronism possibly due to mineral corticoid-responsive hyponatremia of the elderly.

Activities of Daily Living↗
PubMed2006

[Relation between gene polymorphism and acute coronary syndrome].

The acute coronary syndrome, consisting of myocardial infarction and unstable angina, is the most important manifestation of coronary disease and is characterized by atherosclerotic plaque disruption and coronary thrombosis. In the coronary vessel wall, this process contains abnormalities of extracellular matrix, fibrinolytic system, endothelial function, and, possibly, vascular inflammation. Potentially thousands of genes are relevant to this apparently complex disease. Although many risk factors are intercorrelated, raising the possibility of a higher level of genetic control by a small number of master genes that control fundamental physiological systems. Such genes are likely to be relevant to the combined processes of plaque instability and coronary thrombosis.

Angina, Unstable↗
PubMed2005

A novel alternative splice variant of nicastrin and its implication in Alzheimer disease.

Nicastrin interacts with gamma-secretase complex components predominantly via the N-terminal third of the transmembrane domain. The authentic transmembrane domain is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex. In this study, we have identified a novel alternatively spliced transcript of nicastrin in human brain tissue. This transcript (NCSTN-DeltaE16) lacks exon 16 of nicastrin mRNA, which leads to deletion of 71 amino acids just upstream of its transmembrane domain. Its expression pattern was analyzed in the hippocampus of patients with pathologically diagnosed Alzheimer disease (cases) and non-Alzheimer dementia (controls). In patients with the APOE-epsilon4 allele, the frequency of Alzheimer disease appeared to be increased in the NCSTN-DeltaE16-positive group, but the association was not statistically significant. In conclusion, the expression of NCSTN-DeltaE16 transcript may confer some additional risk for developing Alzheimer disease beyond the risk due to ApoE-epsilon4 allele. Further investigation in larger scale population would be necessary to address its potential implication in Alzheimer disease.

Age of Onset↗
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

Lymphocyte-specific protein tyrosine kinase is a novel risk gene for Alzheimer disease.

Lymphocyte-specific protein tyrosine kinase (LCK) is a lymphoid-specific, Src family protein tyrosine kinase that is known to play a pivotal role in T-cell activation and interact with the T-cell coreceptors, CD4 and CD8. It has been shown to be significantly down-regulated in Alzheimer disease (AD) hippocampus compared with non-demented controls. Furthermore, it is located in a previously identified genetic linkage region (1p34-36) associated with AD. Therefore, we consider it to be a candidate gene for AD. We examined the relationship between AD and the LCK and apolipoprotein E (APOE) genes in 376 AD (including 323 late-onset AD (LOAD) cases and 53 early-onset AD (EOAD) cases) and 378 non-demented controls using a single nucleotide polymorphism (SNP). The polymorphism in intron 1 (+6424 A/G) was significantly associated with AD risk. The odds ratio (OR) for total AD associated with the GG genotype was 1.41 (95% CI=1.06-1.87) and that for LOAD was 1.37 (95%CI=1.02-1.85), while that for APOE-epsilon4 was 5.06 (95% CI=3.60-7.12). In the APOE-epsilon4 non-carrier subgroup, the GG genotype also showed significant association (OR=1.66; 95% CI=1.16-2.38). These results indicate that the LCK is a novel risk gene for AD regardless of the APOE genotype.

Age of Onset↗
PubMed2005

Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) in patients with coexistent hypertrophic cardiomyopathy and coronary spastic angina.

Coronary vasospasm appears to play a significant role in the etiology of myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM). Furthermore, the management of patients with coexistent HCM and coronary spastic angina (CSA) presents a therapeutic challenge. The purpose of this study was to examine the Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene to determine whether this polymorphism was associated with susceptibility to CSA in patients with HCM. The eNOS gene polymorphism (Glu298Asp) was genotyped in 150 HCM patients by the TaqMan chemical method. Patients were classified into group A (n=12) if they had CSA provoked by intracoronary acetylcholine, and group B (n=138) if they did not. In group A, the frequency of Glu/Glu, Glu/Asp, and Asp/Asp genotypes was 5 (41.7%), 6 (50%), and 1 (8.3%), respectively. In group B, it was 119 (86.2%), 17 (12.3%), and 2 (1.5%), respectively. The frequency of the Asp298 variant was significantly higher in group A than in group B (P<0.001). Multivariate logistic regression analysis showed that the Asp298 variant was a significant risk factor for CSA (odds ratio 11.8; P<0.001) that was independent of age, gender, smoking status or body mass index. Significantly more drugs were used by the patients in group A than those in group B and the patients with the Asp298 variant were treated with significantly more drugs than those without it. In conclusion, the Asp298 variant of the eNOS gene may be associated with CSA in HCM patients. HCM patients with CSA or the Asp298 variant may need more drugs to relieve their symptoms.

Amino Acid Substitution↗
PubMed2005

Identification of hippocampus-related candidate genes for Alzheimer's disease.

Alzheimer's disease (AD) is a complex multifactorial disease in which many genetic and environmental factors are involved. We performed an association study using 376 AD patients and 376 control subjects. We studied 35 single nucleotide polymorphisms in 35 genes that were significantly downregulated or upregulated only in the AD hippocampus compared with control and found that 9 single nucleotide polymorphisms were associated with AD. Our data indicated that single nucleotide polymorphisms could highly reflect differences in gene expression. Furthermore, an intronic polymorphism (+9943T/C) in POU2F1 was most significantly associated with AD (p = 0.0007). Our results suggest that POU2F1 is a candidate gene for AD.

Aged↗
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↗