PubMed Health⌕ Search

Biomedical subjects

T Arinami

Publications and source records attributed to T Arinami.

At least 55 records · Page 3Linked to original sources
PubMed2000

Linkage of human narcolepsy with HLA association to chromosome 4p13-q21.

Although narcolepsy is highly associated with human leukocyte antigen (HLA) DQ6/DQB1*0602 and/or DR2/DRB1*1501, most individuals with the HLA haplotype are free of narcolepsy. This indicates that HLA alone makes a relatively small contribution to the development of narcolepsy and that a non-HLA gene(s) can contribute to the genetic predisposition even in narcoleptic cases with HLA association. We conducted a genome-wide linkage search for narcolepsy in eight Japanese families with 21 DR2-positive patients (14 narcoleptic cases with cataplexy and 7 cases with an incomplete form of narcolepsy). A lod score of 3.09 suggested linkage to chromosome 4p13-q21. A lod score of 1.53 was obtained at the HLA-DRB1 locus, though this lod score may be biased since all the affected patients and many of the family members were DR2-positive. No other loci including hypocretin, hypocretin receptor 1, and hypocretin receptor 2 had lod scores greater than 1.0. The present study suggests that chromosome 4p13-q21 contains a second locus for HLA-associated human narcolepsy.

Chromosome Mapping↗
PubMed2000

Significant evidence for linkage of febrile seizures to chromosome 5q14-q15.

Febrile seizures (FSs) represent the most common form of childhood seizure. In the Japanese population, the incidence rate is as high as 7%. It has been recognized that there is a significant genetic component for susceptibility to this type of seizure. Two putative FS loci, FEB1 (chromosome 8q13-q21) and FEB2 (chromosome 19p), have been mapped. Furthermore, a mutation in the voltage-gated sodium (Na(+))-channel beta1 subunit gene ( SCN1B ) at chromosome 19q13.1 was identified in a family with a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS(+)). These loci are linked to some large families. In this study, we conducted a genome-wide linkage search for FS in one large family with subsequent linkage confirmation in 39 nuclear families. Significant linkage was found at D5S644 by multipoint non-parametric analysis using GENEHUNTER ( P = 5.4 x 10(-6)). Estimated lambda(s)at D5S644 was 2.5 according to maximum likelihood analysis. Significant linkage disequilibria with FS were observed at the markers D5S644, D5S652 and D5S2079 in 47 families by transmission disequilibrium tests. These findings indicate that there is a gene on chromosome 5q14-q15 that confers susceptibility to FSs and we call this gene FEB4.

Child, Preschool↗
PubMed2000

The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia.

Preeclampsia is associated with thrombosis of the intervillous or spiral artery. A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 (PAI-1) gene is suggested to be involved in regulating the synthesis of the inhibitor, 4G allele, being associated with the enhanced gene expression and plasma PAI-1 levels. We assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI-1 gene in 115 preeclamptic patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of the homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women (P = 0.04) or in the healthy volunteers (P = 0.02). The 4G allele frequency was also significantly higher in the patients than in the control group of pregnant women (P = 0.03) and in the healthy volunteers (P = 0.02). These results suggest that the presence of the 4G/4G genotype of the PAI-1 gene is one of the risk factors for preeclampsia.

Alleles↗
PubMed2000

WFS1 gene mutation search in depressive patients: detection of five missense polymorphisms but no association with depression or bipolar affective disorder.

BACKGROUND: Wolfram syndrome (WFS) is an autosomal recessive neurodegenerative disorder. Recently, the WFS1 gene was isolated, and approximately 80% of the mutations responsible for WFS were found in exon 8 of WFS1. It has been noted that heterozygous carriers of the WFS gene are 26-fold more likely to be hospitalized for depression, and it has been estimated that approximately 25% of all people hospitalized for depression may carry the WFS gene(s). METHODS: We searched for mutations in exon 8 of WFS1 in 30 depressive patients with a history of hospitalization and whose age at onset was under 40 years. We also examined 47 bipolar affective patients and 62 control subjects for an association. RESULTS: A were detected. Four of the six were novel. No nonsense or frameshift mutation was detected. Genotypic and allelic distributions were similar between the depressive patients and the controls. No association with bipolar affective disorder was suggested. LIMITATIONS: Because of the small sample size, the probability of finding at least one patient with WFS-responsible mutation(s) was 70% if depression is associated with WFS1 mutation(s) in 5% of patients. CONCLUSION: It is not likely that WFS1 mutations are responsible for as much as 25% of depressive illness.

Adult↗
PubMed2000

Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait.

Polymorphism in the human dopamine D4 receptor gene (DRD4) exon III has been associated in some but not all studies of the human personality trait of Novelty Seeking. We searched for polymorphisms in the 5' region of DRD4 and identified six polymorphisms as follows: -1217G Ins/Del, -809G/A, -616C/G, -603T Ins/Del, -602(G)8-9, and -521C/T. Associations between these polymorphisms and personality traits measured by the Temperament and Character Inventory (TCI) were investigated in 86 healthy Japanese volunteers. The -521C/T polymorphism was significantly associated with Novelty Seeking (P = 0.0001). Subjects with the C/C genotype exhibited the highest Novelty Seeking scores and those with the T/T genotype exhibited the lowest. A transient expression method revealed that the T variant of the C-521T polymorphism reduces transcriptional efficiency. The present study suggests a contribution of dopamine D4 receptor availability to individual differences in Novelty Seeking behavior. Molecular Psychiatry (2000) 5, 64-69.

Adolescent↗
PubMed2000

Mutation and association analysis of the 5' region of the dopamine D3 receptor gene in schizophrenia patients: identification of the Ala38Thr polymorphism and suggested association between DRD3 haplotypes and schizophrenia.

Although the association between the Ser9Gly polymorphism of the dopamine D3 receptor gene (DRD3) and schizophrenia has been investigated by many research groups, it is not known whether the Ser9Gly polymorphism alone or a variation in linkage disequilibrium may effect susceptibility to schizophrenia. We searched the 5' region of the DRD3 gene and found three novel polymorphisms: -712G/C, -205A/G, and Ala38Thr. The Ala38Thr polymorphism is located in the first transmembrane region and is conserved in the monkey, mouse, and rat. Case-control comparisons in 153 Japanese schizophrenia patients and 122 Japanese controls did not suggest an association between Ala38Thr and schizophrenia. However, there was a marginally significant association between the Ser9 allele of the Ser9Gly polymorphisms and schizophrenia (P = 0.02). Furthermore, there was a highly significant association between haplotypes of the -712G/C, -205A/G, and Ser9Gly polymorphisms and schizophrenia (P = 0.0007, corrected P = 0.007). These positive findings were replicated in an additional 99 Japanese schizophrenia patients and 132 controls (P = 0.04 and 0.0004, respectively). The most allelic differences of the Ser9Gly polymorphism between patient and control groups arose from the chromosome carrying specific alleles of the other three polymorphisms. This study indicates unknown variant(s) in linkage disequilibrium with the DRD3 haplotypes associated with schizophrenia.

5' Untranslated Regions↗
PubMed2000

Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma.

BACKGROUND: IL-4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL-4 gene cluster and asthma and/or asthma-related traits. Interferon regulatory factor 1 (IRF-1) is located approximately 300 kb telomeric to IL-4 and recent study reveals that IRF-1 deficiency results in an elevated production of Th2-related cytokines and a compensatory decrease in the expression of native cell- and Th1-related cytokines. OBJECTIVE: To determine if there are any mutations associated with the development of atopy and asthma present in the coding exons and 5' flanking region of the IRF-1 gene. METHODS AND RESULTS: We have screened the promoter and coding regions of the IRF-1 gene in atopic asthmatics and controls by SSCP method. We found three novel nuclear variants (the -300G/T and 4396 A/G polymorphisms and the 6355G > A rare variant) in the IRF-1 gene. No variants causing amino acid alterations of IRF-1 were detected. The -300G/T polymorphism was in nearly complete linkage disequilibrium with the 4396 A/G polymorphism. An association between the 4396 A > G polymorphism and atopy/asthma was examined by transmission disequilibrium test in 81 asthmatic families. Either of 4396 A or 4396G alleles was not significantly preferentially transmitted to atopy- or asthma-affected children. CONCLUSION: The IRF-1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population.

Adolescent↗
PubMed2000

A contribution to genome-wide association studies: search for susceptibility loci for schizophrenia using DNA microsatellite markers on chromosomes 19, 20, 21 and 22.

As an initial step for genome-wide association studies, we sought an association between schizophrenia and 34 microsatellite markers on chromosomes 19, 20, 21 and 22 by a case-control design. The samples examined for an association were 168 schizophrenic patients and 146 control subjects in the Japanese population. The allele distribution of the 34 loci differed significantly between Japanese and French populations. Significant deviation from the Hardy-Weinberg equilibrium was observed at D19S209 and D21S1256 in the control subjects. Case-control comparisons of the initial screening revealed a significant difference in allele frequency at D20S95 and a trend of difference at D20S118. To confirm these possible associations, additional samples consisting of 110 schizophrenic patients and 116 control subjects were examined, and an association between D20S95 and schizophrenia was confirmed (corrected P value after Bonferroni correction, 0.00035). D20S95 is located close to the gene (CHGB) encoding chromogranin B. These findings suggest that CHGB could be an important candidate gene involved in the development of schizophrenia.

Case-Control Studies↗
PubMed2000

Association study between genetic polymorphisms in the 14-3-3 eta chain and dopamine D4 receptor genes and alcoholism.

BACKGROUND: The dopaminergic system may be involved in the development of alcoholism. As part of our ongoing studies on the association between alcoholism and dopaminergic genes, we report herein a mutation analysis of the 14-3-3 eta chain gene (YWHAH) and an association study between alcoholism and the YWHAH and dopamine D4 receptor gene (DRD4) polymorphisms. METHODS: Nucleotide mutations were investigated using single-strand conformation polymorphism methods. Associations were analyzed using a case-control design involving 185 Japanese alcoholics and 286 Japanese controls. RESULTS: Five polymorphisms, -147G>A, -134(GCCTGCA)2-4, IVS1+31(G)7-8, IVS1+73-74ins(G), and 753A>G, were detected on the YWHAH, and three of them were novel. No significant associations were found between alcoholism and these polymorphisms or two additional polymorphisms on DRD4 exon III and DRD4 -521C/T. CONCLUSIONS: YWHAH and DRD4 do not appear to play a major role in the development of alcoholism.

14-3-3 Proteins↗
PubMed2000

[Turner syndrome].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1999

A genetic polymorphism in the promoter region of DRD4 associated with expression and schizophrenia.

The human dopamine D4 receptor gene (DRD4) is an important candidate gene for schizophrenia. We identified a novel -521C>T polymorphism in the 5'-promoter region of DRD4. A transient expression method revealed that the T allele of this polymorphism reduces the transcriptional efficiency by 40% compared with the C allele. This polymorphism is of interest because of reported elevation of D4-like sites and DRD4 mRNA in the postmortem schizophrenic brain. The C allele frequency was significantly higher in 252 Japanese schizophrenics (0.48) than in 269 Japanese controls (0.41) (p = 0. 02) [odds ratio = 1.35 (95% confidence interval 1.05 - 1.72)]. Although the association is weak and should be considered tentative until other studies replicate it, this polymorphism provides a tool with the potential to examine whether DRD4 is related to susceptibility to and neuroleptic response in schizophrenia.

Adult↗
PubMed1999

No association between C-45T polymorphism in the Sp1 binding site of the promoter region of the cholecystokinin gene and alcoholism.

The activity of dopamine-containing neurons in the ventral tegmental area and nucleus accumbens may play a role in alcoholism. Cholecystokinin (CCK) co-exists in a large proportion of A10 dopamine neurons to exert some effect on dopamine-induced behavior. Recently, a C-45T polymorphism was discovered in the Sp1 binding site in the CCK gene promoter region. We investigated an association between the polymorphism and alcoholism in 209 Japanese DSM-III-R alcoholics and 113 Japanese control subjects. The patients and the control subjects had similar allele and genotype frequencies: the T allele frequencies were 0.27 in the patients and 0.28 in the control subjects and the CC, CT, and the TT genotype frequencies 0.53, 0.39, and 0.08 in the alcoholics and 0.53, 0.37, and 0.10 in the control subjects. Frequencies of clinical characteristics of Feighner's criteria for the lifetime diagnosis of alcoholism were not significantly different among the patient groups divided by the genotype. These findings indicate that the polymorphism has no major effect on the etiology of alcoholism.

Adult↗
PubMed1999

The 5' region of the tryptophan hydroxylase gene: mutation search and association study with alcoholism.

A deficiency in the serotonergic system has been suggested as a negative reinforcer in alcoholism. Tryptophan hydroxylase (TPH) is critical in the fine-tuning of serotonergic neurotransmission. We observed a significantly high frequency of the A allele of the IVS7+218A>C polymorphism in intron 7 of the TPH gene in Japanese alcoholics with histories of drinking-related antisocial behaviors compared with that of Japanese controls (p = 0.006). However, this polymorphism is intronic, and a study of TPH mRNA did not detect aberrant splice products or polymorphic nucleotides linked to this polymorphism. Therefore, we screened for variations in the promoter and 5'-untranslated region of the gene. Three novel variants/polymorphisms, -1066G>A in the 5' flanking region, IVS1B+23(GTTTT)4-5 in intron 1B, and IVS1C+50T>C in intron 1C, were identified. The -1066G>A and IVS1C+50T>C polymorphisms were in modest linkage disequilibrium with the IVS7+218A>C polymorphism. However, no significant association was found between the three novel polymorphisms and alcoholism. Although our findings reiterate that TPH may play some role in the genetic predisposition to alcoholism, the mechanism remains unknown.

Adult↗
PubMed1999

No association between atopic asthma and a coding variant of Fc epsilon R1 beta in a Japanese population.

Susceptibility to atopic diseases is known to involve genetic factors. The Gly237 allele of a polymorphism (Glu237Gly) of the Fc epsilon R1 beta gene is reportedly associated with atopic asthma in Japanese. To confirm this association, we conducted transmission disequilibrium tests in 76 families identified through atopic asthmatics. A case-control study was also carried out in atopic asthmatic subjects and non-atopic controls. The Gly237 allele was not preferentially transmitted to atopic asthma-affected offspring. Neither the Gly237 allele nor the Gly237/Gly237 + Glu237/Gly237 genotypes were significantly more prevalent in the atopic asthmatics than in the controls. This study failed to confirm a substantial role of the Gly237Glu polymorphism of the Fc epsilon R1 beta gene in the genetic predisposition for atopic asthma in this Japanese population.

Amino Acid Substitution↗
PubMed1999

Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism.

Human dopamine transporter gene (DAT1) has a variable number of tandem repeats (VNTR) in its 3'-untranslated region (UTR). The association between the VNTR polymorphism and neuropsychiatric disorders has been studied, but their relationship is still unclear. Here we identified a novel polymorphism in the 3'-UTR of the DAT1 gene, G2319A, and a significant association between the polymorphism and alcoholism was observed in both genotypic and allelic frequencies (P = 0.040 and 0.019, extended Fisher's exact test, respectively). There was a significant gene dose effect on the risk for alcoholism associated with the 2319-A allele (chi2 = 6.16, df = 2, P = 0.046, linearity tendency test: Cochranq-Armitage analysis). Moreover, in the haplotype analysis with G2319A- and VNTR-polymorphisms, a positive gene dose efffect on the risk with the A10 allele (P = 0.044, linearity tendency test) and a negative gene dose effect with the G10 allele (P = 0.010, linearity tendency test) for alcoholism were significantly detected. Odds ratio for alcoholism with the A10 and G10 alleles were 1.76 (1.12-2.76) and 0.53 (0.32-0.79), respectively. These results indicate that the DAT1 gene may confer vulnerability to alcoholism.

3' Untranslated Regions↗
PubMed1999

Lack of association of atopy/asthma and the interleukin-4 receptor alpha gene in Japanese.

BACKGROUND: Susceptibility to the development of atopic diseases is known to involve genetic factors. Several investigators have reported the interleukin-4 (IL-4) receptor alpha gene to be involved in the development of atopy. Recent study has shown that the R allele of a polymorphism in the IL-4 receptor alpha chain gene (Q576R) to be associated with atopy. OBJECTIVE: The objective of this study was to evaluate the possible role of the IL-4 receptor alpha gene in modulating allergic response and asthma in the Japanese population. METHODS: We conducted linkage analysis using microsatellite markers flanking the IL-4 alpha receptor gene in 82 families ascertained through asthmatic children. The IL-4 receptor Q576R polymorphism was also genotyped by PCR-restriction fragment length polymorphism analysis. RESULTS: We did not find evidence for linkage of the asthma and atopy phenotypes with the markers D16S298 and D16S403 (P = 0.10 and P = 0.56, respectively, for the atopy phenotype and P = 0.17 and P = 0.60, respectively, for the asthma phenotype). The IL-4 receptor R576 allele was not preferentially transmitted to atopy- or asthma-affected children (chi2 = 1.67, P = 0.24 for atopy and chi2 = 0.91, P = 0.40 for asthma). In addition, the prevalence of the R576 allele among parents with and without atopy was similar, 20 of 81 (24.7%) parents with atopy and 22 of 77 (28.6%) parents without atopy. CONCLUSION: Our findings indicate that the IL-4 receptor alpha gene does not exert a substantial influence on the inheritance of atopy or asthma in this Japanese population.

Adolescent↗
PubMed1999

Supportive evidence for contribution of the dopamine D2 receptor gene to heritability of stature: linkage and association studies.

Increases in height were reported in children chronically exposed prenatally and postnatally to D2 receptor-blocking drugs. A possible haplotypic association between stature and the DRD2 gene was also reported. In this study, we examined linkage between stature and DRD2 by genotyping a dinucleotide repeat polymorphism in 79 sib-pairs aged 8-17 years. An association between stature and a putative functional polymorphism in the promoter region of the DRD2 gene was examined in the sib-pairs and in 125 unrelated male adults. All the subjects were Japanese. Linkage (p = 0.004, SIBPAL) and an association (p = 0.009, paired t-test, in the sib-pairs; p = 0.006, ANOVA, in the adults) with stature were suggested. These findings indicate that DRD2 is one of the genes that contribute to heritability of stature.

Adolescent↗