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T Arinami

Publications and source records attributed to T Arinami.

At least 73 records · Page 4Linked to original sources
PubMed1999

Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26.

Moyamoya disease is characterized by bilateral stenosis and/or occlusion of the terminal portion of the internal carotid artery. Moyamoya disease is prevalent among patients <10 years of age. Although most cases appear to be sporadic, approximately 10% occur as familial cases. The incidence of familial cases has been increasing because noninvasive diagnostic equipment, such as magnetic-resonance imaging and magnetic-resonance angiography, can detect the disease in almost all affected patients, including asymptomatic patients, during screening studies. In this study, we performed a total genome search to identify the location of a familial moyamoya disease gene in 16 families, assuming an unknown mode of inheritance. A linkage was found between the disease and markers located at 3p24.2-26. A maximum NPL score of 3.46 was obtained with marker D3S3050. This is the first genetic locus found to be involved in the molecular pathogenesis of familial moyamoya disease.

Base Sequence↗
PubMed1999

Frequent occurrence of hypoalphalipoproteinemia due to mutant apolipoprotein A-I gene in the population: a population-based survey.

To determine the frequency of familial hypoalphalipoproteinemia in the general population due to mutation of the apolipoprotein A-I (apo A-I) gene, we analyzed sequence variations in the apo A-I gene. The subjects were 67 children with a low high-density lipoprotein (HDL) cholesterol level (</=38 mg/dl, below the fifth percentile in the population of this study) who were screened from 1254 schoolchildren through a school survey. Four different mutations with deleterious potential, three frameshifts and one splice site mutation, were identified in four of the subjects. The plasma apo A-I levels of the four children with apo A-I gene mutations were reduced to approximately half of the normal levels and were below the first percentile of the general population distribution (80 mg/dl). Thus, the frequency of hypoalphalipoproteinemia due to a mutant apolipoprotein A-I gene was estimated at 6% (95% CI: 2.4-14. 4%) in the subjects with low HDL cholesterol levels and 0.3% (95% CI: 0.1-0.8%) in the Japanese population. This suggests that familial hypoalphalipoproteinemia due to apo A-I gene mutations is relatively common.

Adolescent↗
PubMed1999

Linkage and association of atopic asthma to markers on chromosome 13 in the Japanese population.

Chromosome 13 contains several candidate genes for asthma and atopy, and markers on this chromosome have been shown to be linked to phenotypes of atopy or asthma in two genome-wide searches. We conducted a linkage study for atopic asthma using markers spanning the whole of chromosome 13 in Japanese families ascertained through asthmatic children and examined associations of atopic asthma with markers where linkage was suggested. Data were analysed using MAPMAKER/SIBS for the multipoint lod score (MLS) analysis and SIB-PAIR for the transmission dis-equilibrium test (TDT). Three peaks which exceeded a lod score of 1.0 were observed (MLS 2.4 between D13S175 and D13S217, MLS 2.0 between D13S153 and D13S156, and MLS 1.4 between D13S285 and D13S293). The global TDT for atopic asthma was significant for the marker D13S153 ( P = 0.0065) and the 96 bp allele of D13S153 was preferentially transmitted to atopic asthma-affected children ( P = 0.0009, Bonferroni correction 5% = 0. 0037, 1% = 0.00072). These findings indicate that genes on chromosome 13 may play an important role in the development of atopy or asthma across various populations.

Adolescent↗
PubMed1999

Association study between high and low activity polymorphism of catechol-O-methyltransferase gene and alcoholism.

Catechol-O-methyltransferase (COMT) is a key modulator of dopaminergic and noradrenergic neurotransmission. There is a functional polymorphism of the COMT gene, Val108Met in the soluble form of the enzyme (Val158Met in the membrane-bound form). Involvement of the dopaminergic systems in alcoholism has been suggested in mice and humans. We examined associations between this polymorphism and alcoholism in 175 Japanese alcoholics and 354 age- and gender-matched Japanese controls. No significant difference in the allelic distributions in alcoholics and controls and no significant associations between antisocial behaviors in alcoholics and this polymorphism were observed. Therefore, the COMT gene is not likely to play a significant role in alcoholism.

Adult↗
PubMed1999

No association between atopy/asthma and the ILe50Val polymorphism of IL-4 receptor.

Susceptibility to atopic diseases is known to involve genetic factors. The interleukin-4 (IL-4) receptor- alpha gene (IL4R) reportedly is involved in the development of atopy. A recent study has shown the Ile50 allele of a polymorphism (Ile50Val) of IL4R to be associated with atopy. The objective of this study was to replicate this association and confirm the possible role of the Ile50Val polymorphism of IL4R in the etiology of atopic asthma in a Japanese population. We conducted a transmission disequilibrium test in 86 families identified through asthmatic children. A case-control study was also carried out using both atopic and control subjects. The IL4R Ile50Val polymorphism was genotyped by a PCR-restriction fragment length polymorphism method using an intronic upstream primer. The IL4R Ile50 allele was not preferentially transmitted to atopy- or to asthma-affected children. Neither the Ile50 allele nor the Ile50/Ile50 genotype was more prevalent in the atopic subjects than in the control subjects. Our findings indicate that the Ile50Val polymorphism of IL4R does not play a substantial role in genetic predisposition for the etiology of atopy or asthma in this Japanese population.

Adolescent↗
PubMed1999

A synergistic effect of serotonin transporter gene polymorphism and smoking in association with CHD.

Serotonin induces vasoconstriction in the presence of atherosclerotic lesions. Platelets acquire serotonin from the extracellular space by serotonin transporter and release it following aggregation. There is a functional polymorphism in the serotonin transporter (5-HTT) gene promoter associated with transcriptional efficacy and plasma serotonin levels. To examine whether the polymorphism is associated with coronary heart disease (CHD) in the Japanese, we analyzed 144 male CHD patients with an onset age before 65 and 222 apparently healthy men. The L allele was observed significantly more frequently in the CHD patients (26%) than in the control subjects (19%); the odds ratio was 1.48 (p <0.03). A significant interaction between the polymorphism and smoking was observed for CHD (p = 0.03), suggesting that the two have a synergistic effect on CHD. Odds ratio of the combination of the L allele and smoking was 1.95 (p <0.003). The 5-HTT gene promoter polymorphism may play a role in susceptibility to CHD, particularly when it is combined with smoking.

Adult↗
PubMed1999

Association between drinking-related antisocial behavior and a polymorphism in the serotonin transporter gene in a Japanese population.

BACKGROUND: Involvement of the serotoninergic system (S/S) in alcoholism has been suggested in both mice and humans. Previous studies have suggested the S/S genotype of the serotonin transporter gene promoter polymorphism to be associated with severe alcohol dependence marked by severe withdrawal symptoms. It has also been associated with alcoholics who exhibit a dissocial personality disorder. METHODS: We examined the polymorphism in 166 Japanese alcoholics who experienced withdrawal seizure or delirium and 290 Japanese controls. RESULTS: The S/S genotype was not increased in the patients. Exploratory analyses showed significantly less frequent S allele and S/S genotype frequencies in the alcoholics with a history of drinking-related arrests than in the controls (p = 0.009 and p = 0.03, respectively), perhaps reflecting previously reported harm avoidance personality traits associated with S/S. Alcoholics with the L allele had a significantly earlier onset of alcohol dependence than those with the S/S genotype (p = 0.01). CONCLUSIONS: The present study failed to provide supportive evidence for an association of the S/S genotype with severe alcoholism marked by physical withdrawal symptoms or with antisocial behaviors among the Japanese. Although our data support involvement of the central serotoninergic system in some types of alcoholism, the potential association findings of this study emerged as only exploratory and, therefore, should be understood as tentative until replicated in other studies.

Adult↗
PubMed1999

Association between serotonin transporter gene polymorphism and smoking among Japanese males.

The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine. Compared with the L allele, the S allele of the polymorphism in the upstream regulatory region of the serotonin transporter gene is associated with decreased transcription efficiency of the 5-HTT gene promoter. We examined this polymorphism in a Japanese population consisting of 387 males from two different areas in Japan. The L allele was observed significantly more often in smokers (21%) than in nonsmokers (lifetime nonsmokers + ex-smokers, 14%; P = 0.005). The presence of the L allele (the L/L + L/S genotypes) was also significantly increased in smokers (37%) compared with that in nonsmokers (24%; P = 0.003). The present study suggests that individuals with the S/S genotype are less inclined to smoke and/or can more easily stop smoking than others, supporting a role of the serotoninergic system in smoking behavior.

Adult↗
PubMed1998

Association between polymorphisms in the type 1 sigma receptor gene and schizophrenia.

Several antipsychotic agents such as haloperidol and rimcazole are known to bind to sigma receptors with high affinity, and evidence for a potential link between sigma receptors and the etiology of schizophrenia has been reported. The present study was conducted to systematically search for nucleotide variants of the type 1 sigma receptor gene in 48 schizophrenics. Two polymorphisms were found: GC-241-240TT in the 5' flanking region and Gln2Pro. These two polymorphisms were in nearly complete linkage disequilibrium with each other. The Pro2 variant of the Gln2Pro polymorphism changes the endoplasmic reticulum retention signal motif. These polymorphisms were examined in an extended sample of schizophrenics (n = 308) and controls (n = 433) and a significant association between the presence of the TT/Pro2 haplotype and schizophrenia was observed (odds ratio = 1.27, P = 0.04).

Adolescent↗
PubMed1998

Silent lacunar infarction on magnetic resonance imaging (MRI): risk factors.

We investigated the risk factors for silent lacunar infarction and etat criblé detected by magnetic resonance imaging (MRI). Previous reports have evaluated white matter hyperintensities (WMHs) and periventricular hyperintensities (PVHs) on T2-weighted images, but have not distinguished between lacunar infarcts, état criblé, and leukoaraiosis of Binswanger's type. MRI scans were performed in 270 subjects without neurological deficits over the age of 40 years. They were classified into four subtype groups based on MR findings: normal group (n =60), état criblé group (n=69), silent lacunar infarct/PVH(-) group (n=61), and silent lacunar infarct/PVH(+) group (n=80). We examined the following biochemical variables and other potential risk factors by ordinary logistic regression analysis to identify independent and significant risk factors for silent lacunar infarction: serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, lipoprotein(a), HbA1c, age, sex, systolic blood pressure, diastolic blood pressure, duration of hypertension, family history, smoking habits, alcohol intake, obesity (body mass index), and atrial fibrillation. Subjects in the silent lacunar infarct/PVH(-) (P<0.01) and PVH(+) (P<0.001) groups were significantly older than normal subjects. The systolic blood pressure was also significantly higher in the silent lacunar infarct/PVH(-) (P<0.04) and PVH(+) (P<0.01) groups compared with the normal group. The duration of hypertension was significantly longer in the silent lacunar infarct/PVH(+) group (P<0.02). There were no significant differences in other risk factors between the normal group and the other groups. Ordinary logistic regression analysis showed that age (chi-square 51.8, P<0.0001) and systolic blood pressure (chi-square 5.7, P<0.02) were significant and independent risk factors for silent lacunar infarction. Aging and hypertension were shown to be independent risk factors for silent lacunar infarction.

Adult↗
PubMed1998

Systematic search for variations in the tyrosine hydroxylase gene and their associations with schizophrenia, affective disorders, and alcoholism.

Tyrosine hydroxylase is the rate-limiting step in the biosynthesis of catecholamines. To find variants in the tyrosine hydroxylase (TH) gene that are associated with schizophrenia, mood disorders, or alcohol dependence, all of the exons, the exon-intron boundaries, and the 5' promoter region of the TH gene were systematically screened for variants by single-strand conformation polymorphism analysis followed by direct nucleotide sequencing. Source DNAs for sequencing were from 88 Japanese patients comprised of 17 schizophrenics, 21 with mood disorders, and 50 alcoholics. Two novel variants, T-229A and Val468Met, were identified. Case-control comparisons demonstrated that distribution of these two variants were similar in the controls and the three psychiatric groups. Distributions of the previously reported Val81Met polymorphism alleles and the intron 1 TCAT repeat polymorphism alleles were similar in the four subject groups. Our study indicates that the TH gene is not likely to play a major role in the genetic predisposition to schizophrenia, mood disorders, or alcohol dependence.

Adult↗
PubMed1998

Evidence supporting an association between the DRB1 gene and schizophrenia in Japanese.

The authors attempted a replication of earlier studies that detected an association of HLA-DR4 and DR1 with schizophrenia. Japanese patients with schizophrenia (n = 266, DSM-III-R criteria) and Japanese controls (n = 283) were genotyped for DR1 and DR4 alleles using a combination of group-specific polymerase chain reaction (PCR) amplification and PCR-restriction fragment length polymorphism. Significant positive association with HLA-DR1 [odds ratio (OR) = 1.87, corrected p = 0.04] and a negative association with HLA-DR4 (OR = 0.63, corrected p = 0.02) was noted. DR1 and DR4 were independently associated with schizophrenia. The association of the DR1-positive/DR4-negative genotype with schizophrenia was modest (OR = 2.60, 95% confidence intervals = 1.38-4.89, corrected p = 0.008). Thus, these findings support an association of the HLA DRB1 gene locus with schizophrenia in the Japanese population. Since both DR4 and DR1 are positively associated with rheumatoid arthritis, our findings are not simply consistent with the known negative association between schizophrenia and rheumatoid arthritis.

Female↗
PubMed1998

Evidence for linkage between the development of asthma in childhood and the T-cell receptor beta chain gene in Japanese.

Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components, and several candidate genes have been reported to be linked to atopy and asthma. We have examined a linkage between traits of specific IgE responses to the house dust mite and its purified allergens, high total serum IgE levels and asthma, and the markers at the T-cell receptor (TCR) alpha chain gene (TCR-alpha) and beta chain gene (TCR-beta) in Japanese families ascertained through asthmatic children. Affected sib-pair analyses provided evidence for linkage between TCR-beta and nearby markers (D7S684) on chromosome 7q35 and both IgE and asthmatic phenotypes, but no evidence for linkage of IgE responses nor asthma phenotype to TCR-alpha was detected. The results suggest the presence of major gene(s) controlling atopy and asthma susceptibility in TCR-beta and the nearby region.

Adolescent↗
PubMed1998

Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: a case-control study.

A missense variant of the C677T (Ala --> Val) polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) (the T allele) may increase levels of plasma homocysteine. Apolipoprotein E4 increases plasma LDL-cholesterol levels. Increased levels of homocysteine and LDL-cholesterol have been recognized as risk factors for coronary heart disease (CHD). To examine whether the polymorphisms in the MTHFR gene and the APOE gene are associated with CHD in the Japanese, we analyzed 214 CHD patients with an onset age before 65 and 310 apparently healthy persons. In the controls, significantly higher plasma concentrations of homocysteine were observed in the MTHFR TT genotype (15.1+/-6.0 mmol/l) compared with the CT genotype (11.2+/-1.9 mmol/l) and the CC genotype (10.5+/-3.3 mmol/l). The MTHFR TT genotype was significantly more frequent in the CHD patients (28.5%) compared with the control subjects (13.5%); the odds ratio was 2.54 (P < 0.00003). Subjects with the apo E4 allele were significantly more frequent in the CHD group (22.9%) than in the control group (10.0%); the odds ratio was 2.74 (P < 0.00004). Multivariate analysis showed that the TT genotype of MTHFR and the apoE4 allele are independent risk factors for CHD in the Japanese.

Adult↗
PubMed1998

Association of asthma and the interleukin-4 promoter gene in Japanese.

BACKGROUND: Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. Several investigator have linked the interleukin-4 (IL-4) gene and nearby markers located on chromosome 5 to atopy and asthma. Recent study has demonstrated that the T allele of a polymorphism in the IL-4 gene promoter region (C-590T) is associated with elevated levels of total serum IgE. OBJECTIVE: The objective of this study was to evaluate the possible role of this IL-4 polymorphism (C-590T) in modulating the allergic response and asthma in Japanese children. METHODS AND RESULTS: The study was conducted in two different populations: families ascertained through asthmatic children (asthmatic group, 306 members) in whom linkage of asthma and atopy to chromosome 5q31-33 is suggested and a random general population (control group, 215 members). The IL-4 C-590T polymorphism was genotyped by PCR-restriction fragment length polymorphism analysis. Frequency of the T allele was 0.73 in the asthmatic group and 0.70 in the control group. No significant difference in the levels of total serum IgE and specific IgE to house dust mite was observed between subjects with homozygote for the C allele, a heterozygote and a homozygote for the T allele by intrafamilial and interfamilial comparisons. Using the transmission disequilibrium test, however, we found a significantly frequent transmission of the T allele to asthmatic children (chi2=5.72, P=0.023). CONCLUSION: Our data suggest that the IL-4 promoter C-590T polymorphism may be associated with the development of asthma in Japanese children, but not through modulating total serum IgE levels.

Adolescent↗
PubMed1998

Systematic search for mutations in the 14-3-3 eta chain gene on chromosome 22 in schizophrenics.

The brain-rich 14-3-3 protein regulates synthesis and excretion of bioamine by activating tyrosine and tryptophan hydroxylases, and by exocytosis of catecholamines and serotonin. In humans, at least eight subunits of the 14-3-3 protein family have been isolated. The 14-3-3 eta chain gene is located at 22q12.1 to q13.1, one of the chromosome regions identified as possibly linked to schizophrenia. We systematically searched for nucleotide variants in the coding region, 5' and 3' untranslated region, and in the exon-intron boundaries of the genomic 14-3-3 eta gene in 24 schizophrenics and 24 controls. Two polymorphic sites were found: one in the 5' untranslated region and one in the 3' untranslated region. However, no variants predicting amino-acid alterations were observed. Similar allelic and genotypic distributions for both polymorphisms were found in 308 schizophrenics and 135 controls.

14-3-3 Proteins↗
PubMed1998

Subclinical cerebral lesion accumulation on serial magnetic resonance imaging (MRI) in patients with hypertension: risk factors.

OBJECTIVES: We investigated the occurrence in hypertensive patients of new subclinical changes in the brain by serial magnetic resonance imaging (MRI). METHODS: MRI was performed serially in 98 hypertensive subjects without neurologic deficits at least once a year for 3 years. All received antihypertensive medicines Blood pressure, serum lipids, diabetes mellitus, body mass index (BMI), and other clinical factors were correlated with results. RESULTS: Seventy-nine patients had unchanged MRI findings, while 19 developed new lesions (silent lacunar infarct and etat criblé in 3, silent lacunar infarct in 9, and etat criblé in 7). Follow-up systolic blood pressures were significantly higher than individual baselines in the unchanged group, while the follow-up diastolic blood pressures in the new lesion group were significantly lower than in the unchanged group. BMI was significantly lower in the new lesion group. Follow-up HbA1c levels in both groups were significantly higher than at baseline. Diabetes mellitus was significantly more frequent in the new lesion group than in the unchanged group. No significant differences were apparent in serum lipids level, prescribed antihypertensive medications, and other potential risk factors. CONCLUSIONS: New subclinical MRI changes in hypertensive subjects occurred relatively frequently (19 of 98 subjects, or 19.4%). An excessive fall in diastolic blood pressure, diabetes mellitus, and low BMI emerged as candidate risk factors for these changes.

Aged↗