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T Arinami

Publications and source records attributed to T Arinami.

At least 91 records · Page 5Linked to original sources
PubMed1998

Linkage and association of an interleukin 4 gene polymorphism with atopic dermatitis in Japanese families.

We examined linkage between markers at and near the IL4 gene and atopic dermatitis (AD) in 88 Japanese nuclear families. Affected sib pair analysis suggested linkage between the IL4 gene and AD (SPLINK lod=2.28). Transmission disequilibrium testing showed a significantly preferential transmission to AD offspring of the T allele of the -590C/T polymorphism of the IL4 gene (p=0.001). A case-control comparison suggested a genotypic association of the TT genotype with AD (odds ratio=1.88, p=0.01). Since the T allele was reported to be associated with increased IL4 gene promoter activity compared with the C allele, our data indicate that genetic differences in transcriptional activity of the IL4 gene influence AD predisposition, particularly in Japanese, because of a high frequency of the T allele.

Case-Control Studies↗
PubMed1998

Association study between the -141C Ins/Del and TaqI A polymorphisms of the dopamine D2 receptor gene and alcoholism.

Dopamine D2 receptors have been implicated in the biology of alcohol preference. We examined the -141 C Ins/Del polymorphism in the promoter region of the dopamine D2 receptor gene (DRD2) and the DRD2 TaqI A polymorphisms in 209 Japanese alcoholics and 152 age- and sex-matched Japanese controls. The Ins allele was significantly increased in the alcoholics, compared with the controls (p < 0.002, odds ratio = 1.82). The TaqI A1 allele tended to be more frequent in the alcoholics than in the controls (p < 0.04). Linkage disequilibrium between these two polymorphisms was weak (a maximum delta value = 0.13). The -141 C Ins/Del polymorphism may affect the vulnerability for alcoholism presumably through different expression of DRD2 in the Japanese.

Adult↗
PubMed1997

Methylenetetrahydrofolate reductase variant and schizophrenia/depression.

Patients with methylenetetrahydrofolate reductase (MTHFR) deficiency often show psychiatric manifestations. Since a common variant of the MTHFR gene, T677(Ala), responsible for the thermolabile MTHFR with less than 50% specific MTHFR activity, has been reported, we examined whether the T677 allele is associated with psychiatric disorders in an unrelated Japanese population consisting of 297 schizophrenics, 32 patients with major depression, 40 patients with bipolar disorder, and 419 controls. The genotype homozygous for the T677 allele was significantly frequently observed in schizophrenics with an odds ratio of 1.9 (P = 0.0006), and in patients with major depression with an odds ratio of 2.8 (P = 0.005). Our data suggest associations of the MTHFR gene variant with schizophrenia and depression in the Japanese.

Adult↗
PubMed1997

Sequence analysis of long FMR1 arrays in the Japanese population: insights into the generation of long (CGG)n tracts.

The human fragile-X syndrome is associated with expansions of a (CGG)n triplet repeat within the FMR1 gene. Whilst normal FMR1 arrays consist of variable numbers of (CGG)7-13 blocks punctuated with single AGG triplets, unstable arrays contain longer blocks of uninterrupted (CGG)n. The degree of instability, and subsequent risk of expansion to the fragile-X mutation, is dependent upon the length of this uninterrupted repeat. Detailed analyses of normal FMR1 array structures suggest that longer uninterrupted blocks of repeat could arise either through a process of gradual slippage or a more dramatic loss of an intervening AGG triplet. Up to 15% of Japanese and Chinese individuals have FMR1 triplet arrays centred on 36 repeats in length, a modal group not found in Caucasians. As longer FMR1 arrays have been associated with high-risk fragile-X haplotypes in some populations, we investigated the nature of these larger arrays. Sequence analysis revealed that the unusual length is due to the presence of a novel (CGG)6 block within the array. Several haplotypically related arrays contain blocks of (CGG)16 or (CGG)15, consistent with the fusion of adjacent (CGG)9 and (CGG)6 blocks after loss of the intervening AGG triplet. This is compatible with inferences from the Caucasian population that AGG loss is a mechanism by which long blocks of identical repeats are generated.

Dinucleotide Repeats↗
PubMed1997

Abnormal myelination in a patient with ring chromosome 18.

We describe a Japanese boy with ring chromosome 18 in whom abnormal myelination was observed on magnetic resonance imaging. Cytogenetic investigation revealed 46, XY, r(18) (p11.2 q21.33). T2-weighted magnetic resonance imaging scan of the brain demonstrated high signal intensity consistent with abnormal myelination. Microsatellite marker analysis of DNA demonstrated only one copy of the myelin basic protein gene, derived from the mother. The present case indicates that a hemizygous state for the myelin protein gene may be related to the abnormal myelination.

Brain↗
PubMed1997

A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia.

An excess dopaminergic activity may be implicated in the etiology of schizophrenia. Our objective was to identify nucleotide variants in the 5' region of the dopamine D2 receptor gene (DRD2) and to clarify their effects on schizophrenia. We identified two polymorphisms, the A-241G and -141C Ins/Del, by examination of 259 bp in the 5'-flanking region and 249 bp of exon 1 of DRD2. Reporter constructs containing the -141C Del allele cloned into a luciferase reporter plasmid drove 21% (Y-79 cells) and 43% (293 cells) expression compared with the -141C Ins allele. In a case-control study, the -141C Del allele frequency was significantly lower in 260 schizophrenic patients than in 312 controls (OR = 0.60, 95%CI 0.44-0.81, P < 0.001). No significant association was found between the A-241G polymorphism and in vitro luciferase activity, or in allele frequency between the patients versus controls. These findings show that the -141C Ins/Del may be a functional polymorphism in the 5'-promoter region of DRD2 and may affect the susceptibility to schizophrenia.

Adult↗
PubMed1997

An association study between a transcriptional polymorphism in the serotonin transporter gene and panic disorder in a Japanese population.

A polymorphism in the 5' region of the serotonin transporter gene modulates its transcription efficiency. Its short allele has been reported to be associated with neurotic traits. The serotonin transporter is the action site of selective serotonin re-uptake inhibitors, widely used in the treatment of panic disorder. We examined an association between the polymorphism and panic disorder in a case-control study consisting of 66 Japanese patients and 150 controls. The short allele was significantly more frequent in the Japanese than in Caucasians. The patients and the controls had similar allele frequencies, indicating no association between the polymorphism and panic disorder in most Japanese patients.

Adult↗
PubMed1997

Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.

A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, a C to T substitution at nucleotide 677, is responsible for reduced MTHFR activity and associated with modestly increased plasma homocysteine concentrations. Since underlying maternal vascular disease increases the risk of pre-eclampsia, we had the working hypothesis that pre-eclampsia patients would have an increased T677 allele frequency compared with controls. The MTHFR genotypes were determined in 67 pre-eclampsia patients, 98 normal pregnant women, and 260 healthy adults by the PCR/RFLP method. The T677 allele and the genotype homozygous for the T677 allele were significantly increased in the pre-eclamptic group compared with the controls (p < 0.02 and p < 0.004, respectively). The data indicate that the T677 variant of the MTHFR gene is one of the genetic risk factors for pre-eclampsia.

Adult↗
PubMed1997

Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population.

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 in Caucasian populations. We conducted a study of linkage between asthma and markers on chromosomes 5q31-q33 and 11q13 in 68 Japanese families (306 members) by affected sib-pair analysis. Families for the linkage study were ascertained through asthmatic children visiting the allergy clinic. The results provide supportive evidence for linkage between asthma and gene markers in or near the interleukin-4 (IL-4) gene, the IL-9 gene, and D5S393 on chromosome 5q31-q33 (p = 0.0013, p = 0.018, and p = 0.0077, respectively). Linkage between atopic phenotype and these genetic markers was also suggested (p = 0.006, p = 0.01, and p < 0.0001 for atopy, respectively). However, we failed to find evidence for linkage of asthma or atopy to the IgE high-affinity receptor gene on 11q13 (p > 0.1). These findings indicate that beyond ethnicity, there are specific loci that contribute to susceptibility to atopy on chromosome 5q31-q33. In addition, our findings suggest that loci on chromosome 5q31-q33 are linked to the development of asthma in childhood.

Adolescent↗
PubMed1997

The proportion of fetal nucleated red blood cells in maternal blood: estimation by FACS analysis.

The purpose of this study was to determine the proportion of fetal nucleated red blood cells (NRBCs) among enriched NRBCs and to evaluate the effectiveness of enriching NRBCs in maternal blood using fluorescence-activated cell sorting (FACS) to separate NRBCs. The origin of enriched NRBCs was determined using fluorescence in situ hybridization (FISH) methods. Y-specific signals were observed in 4.6 +/- 1.5 per cent of the enriched cells from 14 of 16 (87.5 per cent) pregnant women who gave birth to boys. In this series, the specificity of the fetal sex diagnosis was 100 per cent, the sensitivity 88 per cent, and the negative predictive value 86 per cent. Fetal NRBCs are present in maternal blood and FACS has the potential to enrich fetal NRBCs. Fetal cells were estimated to be enriched more than 10,000-fold in the first trimester and more than 100-fold in the third trimester. Average frequencies of fetal cells in maternal blood were 8.1 x 10(-5) and 1.6 x 10(-5) in the first trimester and the second/third trimesters. However, most of the NRBCs in maternal blood are maternal in origin.

Antigens, CD↗
PubMed1996

An insertion/deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders.

Because of a potent action of angiotensin converting enzyme (ACE) to degrade substance P (SP) and an association of the insertion/deletion (I/D) polymorphism of the ACE gene with ACE activity, an association between the SP level and the ACE I/D polymorphism were examined using 20 human postmortem brain samples. The results showed a significant association between the polymorphism and SP levels in the basal ganglia and substantia nigra, where both ACE and SP concentrate, and a higher SP level in the subjects with the DD genotype than in those with the II genotype, with an intermediate level in heterozygotes. Associations of the polymorphism with schizophrenia and affective disorders were also investigated in 292 unrelated Japanese schizophrenics, 65 patients with affective disorders, and 579 controls. The D allele was significantly more frequent in the patients with affective disorders than in the controls (p < .02), and the DD genotype was significantly more frequent in the patients with affective disorders than in the controls (p < .002). There is no significant difference in the frequencies of the allele and the genotype between the controls and schizophrenics. These results suggest that the ACE I/D polymorphism is one of the genetic factors for an interindividual variability of brain SP levels, and that the ACE polymorphism may contribute to the susceptibility to affective disorders.

Adult↗
PubMed1996

Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders.

The dopamine D2 receptor gene is a candidate gene for schizophrenia because the potency of certain neuroleptics correlates with their affinity for this receptor. Case-control studies in 291 schizophrenics, 78 patients with affective disorders, and 579 controls on an association of a molecular variant of S311C of the dopamine D2 receptor with psychiatric disorders were conducted. The frequency of individuals with S311C was significantly higher in schizophrenics with the absence of negative symptoms (17.1%, P < 0.00001), but similar in schizophrenics with the presence of negative symptoms (5.7%, P = 0.46) when compared with the controls (4.1%). The frequency of S311C was significantly higher in familial schizophrenics from one local area but not in those from other areas. It was significant that S311C was frequently present in patients with mood-incongruent psychotic affective disorders (33.3%, P < 0.0001), but not in those with other affective disorders. These data suggest that S311C might be one of the genetic factors for symptomatic dimensions of delusions and hallucinations and might be involved in underlying clinical heterogeneity in schizophrenia and affective disorders.

Adult↗
PubMed1996

Apolipoprotein(a) and pentanucleotide repeat polymorphisms are associated with the degree of atherosclerosis in coronary heart disease.

To evaluate whether a high level of lipoprotein(a) (Lp(a)) is a risk for the development of coronary heart disease (CHD), 94 Japanese patients and 64 age-matched Japanese controls, diagnosed after coronary angiography (CAG), were analyzed with special reference to the relations between the degree of atherosclerosis, Lp(a) levels and the apolipoprotein(a) (apo(a)) genotypes. the degree of atherosclerosis was evaluated based on CAG findings in the following three ways: the number of diseased vessels, the Gensini score, and the presence or absence of vascular ulcers and/or irregular outlines of coronary stenotic lesions. Apo(a) protein sizes and the pentanucleotide (TTTTA) repeat polymorphism in the 5' control region of the apo(a) gene were analyzed. Multivariate predictors for the number of diseased vessels were, in decreased order of significance, plasma Lp(a) levels, history of smoking, hypertension, diabetes mellitus, and body mass index (BMI). Independent factors associated with the Gensini score were Lp(a) levels, BMI, hypertension, and diabetes mellitus. A negative association of Lp(a) levels with apo(a) protein sizes, and higher Lp(a) levels in those homozygous for an allele with 8 8 (TTTTA)-repeats, was found in both the controls and patients. In decreasing order of significance, apo(a) protein sizes, the degree of atherosclerosis, the genotype of the pentanucleotide repeat, and gender were independent predictors of Lp(a) levels in stepwise regression models. Apo(a) protein sizes were a significant predictor, and the genotype homozygous for the 8 (TTTTA)-repeats was a possible predictor, for the degree of atherosclerosis in CHD. These findings support the notion that a high Lp(a) level is a risk for the development of atherosclerosis in CHD.

Alleles↗
PubMed1996

Failure to find associations of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia.

This study aimed to replicate positive associations between polymorphisms of the neurotrophin-3 gene and schizophrenia. The reported associations, which were the results of searching for mutations in the locus in schizophrenics under the hypothesis of neurodevelopmental etiology of schizophrenia, are that the states carrying the (CA)23 allele of the CA repeat in the first intron have a 2.56-fold increased risk of schizophrenia and those carrying the allele Glu-63 instead of Gly-63 have a 2.6-fold increased risk of schizophrenia with onset before 25 years and with duration of the illness of more than 10 years. We analyzed these polymorphisms in 80 schizophrenics with onset before 25 years of age and with duration of illness of more than 10 years and 80 age-matched psychosis-free controls. With our sample size, there was a 90% chance of detecting odds ratios observed in initial positive reports. We found similar allele and genotype frequencies of both polymorphisms between the schizophrenic and control groups. We failed to support associations between the polymorphisms of the neurotrophin-3 gene analyzed and schizophrenia.

Adult↗
PubMed1996

Sequestration of the short and long isoforms of dopamine D2 receptors expressed in Chinese hamster ovary cells.

The short (D2S) and long (D2L) isoforms of dopamine D2 receptors were stably expressed in Chinese hamster ovary cells, and dopamine-induced sequestration was examined by measuring the loss of binding of the hydrophilic ligand [3H]sulpiride from the cell surface. Dopamine treatment of Chinese hamster ovary cells expressing D2S for 30 min at 37 degrees caused a 43.8 +/- 3.4% decrease in [3H]sulpiride binding activity measured by incubation of the treated cells with [3H]sulpiride at 4 degrees for 4 hr after the dopamine was washed out. The half-life of the decrease in binding was estimated to be 18.7 +/- 1.6 min, and the concentration of dopamine giving a half-maximal effect (EC50) was estimated to be 180 +/- 90 nM. The decrease was reversible, and the binding activity was recovered by washing out the dopamine and incubating the cells at 37 degrees for 30 min but was not reversible when the cells were incubated at 4 degrees. The binding activity of [3H]spiperone, a hydrophobic ligand, was not affected by the dopamine treatment under the same experimental conditions. These results indicate that approximately one half of the D2S receptors undergo agonist-induced sequestration, probably endocytosis, in a reversible and temperature-dependent manner. Sequestration of D2L receptors was not as apparent as that of D2S receptors; the decrease in [3H]sulpiride binding activity was 21.6 +/- 0.9% and the rate of the decrease was delayed, with a half-life of 33.2 +/- 7.8 min, although effective concentrations of dopamine were similar, with EC50 = 170 +/- 50 nM. A D2S receptor variant containing a missense mutation changing Ser311 in the third intracellular loop to cysteine was found to be sequestered to a significantly lesser extent than with wild-type D2S receptors. This finding was discussed with respect to the report that this variant gene is found more frequently in schizophrenic patients than in control subjects.

Animals↗