Biomedical subjects

Takafumi Ishida

Publications and source records attributed to Takafumi Ishida.

At least 19 recordsLinked to original sources

PubMed2006

Association of mu-opioid receptor gene polymorphism A118G with alcohol dependence in a Japanese population.

Ethanol is considered to activate the brain reward system by increasing the release of an endogenous opioid receptor ligand, beta-endorphin. The polymorphism A118G in the mu-opioid receptor gene (OPRM1) causes the amino acid change Asn40Asp and has been reported to affect the affinity of the ligand for the receptor. The association of this polymorphism with the vulnerability to alcohol dependence has been studied in many populations, but not yet in Japanese people. In the present study, we compared the frequencies of the polymorphism OPRM1 A118G between patients with alcohol dependence and healthy control subjects living in a Japanese provincial prefecture. We also genotyped a polymorphism, G1510A, in the acetaldehyde dehydrogenase 2 gene (ALDH2), in which the A allele causes poor metabolism of acetaldehyde, a major metabolite of alcohol. Both OPRM1 118G and ALDH2 1510G were significantly associated with alcohol dependence. These results suggest that OPRM1 118G in addition to ALDH2 1510G might be one of the risk factors for alcohol dependence in Japanese people.

Adult↗

PubMed2006

Analysis of LMP1 variants of EBV in Southern Thailand: evidence for strain-associated T-cell tropism and pathogenicity.

BACKGROUND: The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) has sequence heterogeneity. Some of the variants are associated with altered tumorigenic activity and show geographically specific localization. In Thailand, the EBV genome is frequently detected in circulating T cells of T-cell diseases. OBJECTIVE: To determine the role of EBV LMP1 variation in the genesis of T-cell diseases, we focused on virus factors and analyzed EBV strains in Thailand. STUDY DESIGN: EBV DNA was extracted from 18 healthy individuals and 45 patients with T-cell diseases in Southern Thailand and 30 healthy individuals in Central Thailand. By using PCR-direct sequencing method, nucleotide sequences corresponding to the carboxyl terminus of the LMP1 were determined. RESULTS: Four known strains, B95-8 prototype, China 1, China 2 and Mediterranean (Med) and two novel strains, Southeast Asia 1 (SEA 1) and Southeast Asia 2 (SEA 2) were identified. The prevalence of China 2 strain was significantly different (p=0.006) between Central and Southern Thailand. Higher prevalence (p=0.026) of 30-bp deletion type in the Southern Thais was observed. The LMP1 Med strain was associated with the worse prognosis (p=0.029). Among T-cell diseases patients, CD3(+)-cell oriented infection was recognized in SEA1 strain (p=0.025). CONCLUSION: The distribution of EBV strains may be associated with geographic/ethnic and clinical background in the Thai population. Certain EBV strains defined by their LMP1 sequence may influence cell tropism, disease association, or disease severity.

Amino Acid Sequence↗

PubMed2006

Polymorphisms in the ABO blood group gene in three populations in the New Georgia group of the Solomon Islands.

To examine genetic affinity among Oceanian populations, polymorphisms of exons six and seven of the ABO blood group gene (ABO) were investigated in three populations--Munda town, Paradise village, and Rawaki village--in the New Georgia group of the Solomon Islands. The Munda and Paradise populations consist of Austronesian (AN)-speaking Melanesians; the Rawaki population consists of AN-speaking Micronesians who migrated from the Gilbert Islands to the New Georgia Islands approximately 30 years ago. We recently described the polymorphisms of ABO in three other Oceanian populations--Balopa Islanders (AN-speaking Melanesians), Gidra (non-AN-speaking Melanesians), and Tongans (AN-speaking Polynesians). The results from these six Oceanian populations suggest: (1) the main alleles in Oceanian populations are ABO*A101, ABO*A102, ABO*B101, ABO*O01, and ABO*O02, among which the most predominant is ABO*O01, and (2) there are marked differences in the ABO allele frequency spectrum among Oceanian populations. The different geographical distribution of ABO alleles provides insight into the migration history of AN-speaking populations in Oceania.

ABO Blood-Group System↗

PubMed2006

Coexistence of five G6PD variants indicates ethnic complexity of Phuket islanders, Southern Thailand.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. The prevalence of G6PD deficiency and its molecular basis were studied in Phuket islanders, Southern Thailand. A total of 345 volunteers (123 males and 222 females) were recruited in this study. Infection with Plasmodium falciparum or Plasmodium vivax was not detected in any of these subjects by polymerase chain reaction (PCR)-based diagnosis. G6PD-deficient individuals were identified with the WST-8/1-methoxy PMS method. The molecular basis of G6PD deficiency was investigated by PCR-direct sequencing procedures or PCR-restriction enzyme fragment length polymorphism assays. The numbers of individuals showing severe and mild G6PD deficiency were 14 and 21, respectively. A high prevalence of G6PD deficiency was observed in subjects with Moken (15.4%) or Thai (15.5%) ethnic background. G6PD Mahidol (487G>A) (n=14), G6PD Viangchan (871G>A) (n=11), G6PD Gaohe (95A>G) (n=2), G6PD Kaiping (1388G>A) (n=1), and G6PD Kerala-Kalyan (949G>A) (n=1) were identified. The results suggest that several groups of people of the Asian Continent, such as Burmese, Laotian or Cambodian, Thai and Chinese, participated in the establishment of the ethnic identity of the current ethnic groups of Phuket Island.

Asian People↗

PubMed2006

Identification of novel functional variants of the melanocortin 1 receptor gene originated from Asians.

Human melanocortin 1 receptor (MC1R) is a seven transmembrane G-coupled protein receptor that upregulates the cAMP pathway. Several functional variants of MC1R that show an impaired ability to activate the cAMP pathway are strongly associated with fair skin and red hair in Europeans and European descendants. The sequence variations of the MC1R gene were repeatedly investigated against worldwide populations; however, there was no evidence that functional variant of MC1R exists in non-European descendants. We report the presence of novel functional variants of MC1R with Asian origins. Three novel variants of MC1R, Phe147Delta, Thr157Ile, and Pro159Thr, were identified in our screening for the sequence variations of the MC1R gene against 995 individuals from 30 Asian and Oceanian populations; there was a single case for the Pro159Thr variant allele and two instances of Phe147Delta and Thr157Ile variant alleles. Our pharmacological assay revealed that Phe147Delta, Thr157Ile, and Pro159Thr variant showed similar or more dramatically impaired activities in comparison with Arg151Cys, which is a major functional variant of MC1R in Europeans. These functional variant alleles were geographically localized in relatively high latitudes, which suggest that the adaptation to ambient UV light intensity may play an important role in shaping the geographical distribution of MC1R alleles in Asia and Oceania.

Animals↗

PubMed2006

A SNP in the ABCC11 gene is the determinant of human earwax type.

Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. Here we show that a SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of Asian ancestry. A functional assay demonstrated that cells with allele A show a lower excretory activity for cGMP than those with allele G. The allele A frequency shows a north-south and east-west downward geographical gradient; worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype is retained among various ethnic populations. These suggest that the allele A arose in northeast Asia and thereafter spread through the world. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait.

ATP-Binding Cassette Transporters↗

PubMed2006

Alu-mediated 100-kb deletion in the primate genome: the loss of the agouti signaling protein gene in the lesser apes.

Agouti signaling protein (ASIP) is an endogenous antagonist of melanocortin receptors that controls a wide range of physiological functions. Its central role in regulation of the melanocortin system implied that ASIP has been relevant to the evolution of various physiological traits in primates. In this study, we have tried to determine DNA sequences of the ASIP gene (ASIP) of various simian species to find molecular evolutionary aspects of ASIP. Unexpectedly, we found that the whole coding region of ASIP was missing only from the gibbon genome; gibbons constitute a large group of hominoid species in Southeast Asia. Our analyses revealed that unequal homologous recombination mediated by two AluSx elements erased a approximately 100-kb region including ASIP from the gibbon genome. The data provide new evidence for the significant roles of Alu elements in the dynamic evolution of the primate genome.

Agouti Signaling Protein↗

PubMed2006

Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice.

Bach1 is a transcriptional repressor of heme oxygenase-1 gene (Hmox-1) and beta-globin gene. Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme that degrades pro-oxidant heme to carbon monoxide (CO) and biliverdin/bilirubin, which are thought to mediate anti-inflammatory and anti-oxidant actions of HO-1. In the present study, we investigated the role of Bach1 in tissue protection against myocardial ischemia/reperfusion (I/R) injury in vivo using mice lacking the Bach1 gene (Bach1(-/-)) and wild-type (Bach1(+/+)) mice. In Bach1(-/-) mice, myocardial expression of HO-1 protein was constitutively up-regulated by 3.4-fold compared to that in Bach1(+/+) mice. While myocardial I/R induced HO-1 protein in ischemic myocytes in both strains of mice, the extent of induction was significantly greater in Bach1(-/-) mice than in Bach1(+/+) mice. Myocardial infarction was markedly reduced in size by 48.4% in Bach1(-/-) mice. Pretreatment of Bach1(-/-) mice with zinc-protoporphyrin, an inhibitor of HO activity, abolished the infarction-reducing effect of Bach1 disruption, indicating that reduction in the infarct size was mediated, at least in part, by HO-1 activity. Thus, Bach1 plays a pivotal role in setting the levels of both constitutive and inducible expression of HO-1 in the myocardium. Bach1 inactivation during I/R appears to be a key mechanism controlling the activation level of cytoprotective program involving HO-1.

Animals↗

PubMed2005

Cytochrome P450 2A6 polymorphism in nasopharyngeal carcinoma.

Nitrosamine has been identified as a carcinogen for nasopharyngeal carcinoma (NPC). Here, we investigated if a nitrosamine metabolizing gene, cytochrome P450 2A6 (CYP2A6) played an important role in NPC development. Relationships between the disease and the CYP2A6 were studied in 74 NPC patients and 137 age-matched healthy controls by using PCR-RFLP assay to distinguish between a wide type allele, *1A, and two mutant alleles, *1B and *4C. Overall, a significant association between CYP2A6 polymorphism and NPC development was observed (P<0.05). Individual with mutant alleles had an increased risk for NPC when compared to those with *1A/*1A (OR=2.37, 95% CI=1.27-4.46). In addition, males who carried mutant alleles of CYP2A6 had a fivefold increased risk for NPC when compared with those who carried *1A/*1A genotype (OR=5.02, 95% CI=1.82-14.14). It is thus suggested that CYP2A6 polymorphism may play a crucial role in NPC susceptibility and it may be used as a risk marker for NPC.

Adult↗

PubMed2005

Evidence for recent positive selection at the human AIM1 locus in a European population.

Two missense polymorphisms (E272K and L374F) of the AIM1 locus, encoding a melanocyte differentiation antigen, were shown to have a clear association with human ethnicities. These two nonpathogenic single nucleotide polymorphisms (SNPs) may be associated with human pigmentation variation. In this study, we investigated sequence variation in the coding region and exon-flanking sequence and found low genetic variation only in subjects of European descent. All four statistical tests applied to the 7.55-kb region surrounding the L374F polymorphism detected statistically significant deviations from selective neutrality in Europeans. In addition, haplotype analysis revealed that one haplotype carrying 374F was overrepresented in this population, and the low rate of variation, with some features of selective sweeps, was shown to be statistically significant. These results suggest that positive selection recently has been acting or has acted on at least this region of the melanogenic gene and that an advantageous haplotype spread rapidly in Europe.

Chromatography, High Pressure Liquid↗

PubMed2005

Polymorphism in DNA repair genes and oral squamous cell carcinoma in Thailand.

DNA repair capacity is essential in maintaining cellular functions and homeostasis. However, the repair capacity can be altered based on DNA sequence variations in DNA repair genes and thus may cause cancer susceptibility. We investigated associations between polymorphisms in DNA repair genes and oral squamous cell carcinoma (OSCC) in a Thai population. Nine known single nucleotide polymorphisms (SNPs) in five common DNA repair genes were investigated: XRCC1 (Arg194Trp and Arg399Gln); XRCC3 (Thr241Met); XPC (PAT and Lys939Gln); XPD (exon 6, and Lys751Gln); and MGMT (Trp65Cys and Leu84Phe). We studied 106 cases and 164 healthy controls that were frequency-matched by age (+/-5 years), gender, and cigarette smoking and alcohol drinking habits. The genotype assays were performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The R version 2.0.1 statistical software was applied for statistical analysis of association. Based on multivariate analyses, we found that the variant genotypes with XRCC3 241Met exhibited a >3-fold elevated risk (OR = 3.3, 95% CI = 1.31-8.36, p = 0.01) for OSCC. There was a marginally significant risk observed in variants with XRCC1 194Trp (OR = 1.81, 95% CI = 0.91-3.63, p = 0.09) and XPD exon 6 (OR = 1.71, 95% CI = 0.93-3.16, p = 0.09). Combination of the variant genotypes of these three susceptibility genes was associated with a highly significant risk for OSCC (OR = 9.43, 95% CI = 1.98-44.9, p < 0.01). From further multivariate analyses, the variants with XRCC1 194Trp and possibly XRCC3 241Met interacted with tobacco and alcohol to further increase the risk (OR = 3.37 95% CI = 1.41-8.02, p < 0.01; OR = 2.92, 95% CI = 0.94-9.04, p = 0.06). On the other hand, increased risk was detected in non-betel chewers (OR = 2.88, 95% CI = 1.31-6.31, p < 0.01; OR = 2.61, 95% CI = 0.97-7.11, p = 0.06) who carry the two variant genotypes, respectively. Males with the variants XRCC1 194Trp or XRCC3 241Met had a higher risk of developing OSCC than males with the corresponding wild-type genotypes (OR = 2.72, 95% CI = 1.34-5.52, p < 0.01; OR = 2.95, 95% CI = 1.12-7.75, p < 0.05). Such association was not detected in females. Interestingly, the risk increased in female carriers of XPD exon 6 (OR = 3.93, 95% CI = 1.14-13.6, p < 0.05). We could not demonstrate a significant interaction of these SNPs with age in this study. Our data indicate that the variant genotypes with XRCC3 241Met and possibly XRCC1 194Trp and XPD exon 6 contribute to OSCC development in a Thai population. In addition, these SNPs influence the repair of DNA damage that is caused by environmental risk factors for oral cancer.

Aged↗

PubMed2005

Glucose-6-phosphate dehydrogenase deficiency and Southeast Asian ovalocytosis in asymptomatic Plasmodium carriers in Sumba island, Indonesia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and Southeast Asian ovalocytosis (SAO) caused by a 27-bp deletion in the band 3 gene (Band3Delta 27) are well-documented genetic traits resistant to malarial diseases; however, relationships between these traits and asymptomatic malaria infection hitherto had not been investigated. Filter-blotted blood samples were collected from a total of 210 healthy individuals, 100 males and 110 females, aged 6-17 years, in Sumba island, Indonesia, to survey for the presence of Plasmodium parasites, G6PD activity and the Band3Delta 27 mutation. Presence of P. falciparum and/or P. vivax was identified in 25 subjects (11.9%). In all, 24 subjects (11.4%) showed Band3Delta 27 heterozygously. In males and females, eight and nine subjects, respectively, showed G6PD deficiency. There was no significant difference in the prevalence of asymptomatic malaria infection between individuals with or without these traits (P>0.05). No alterations in the prevalence of asymptomatic malaria infection suggest that parasite invasion into erythrocytes is unlikely to be a target phase in which the two polymorphisms demonstrate possible protective effects against malaria.

Adolescent↗

PubMed2005

Role of the JNK pathway in thrombin-induced ICAM-1 expression in endothelial cells.

OBJECTIVE: Thrombin induces leukocyte adherence to endothelial cells via increased expression of intercellular adhesion molecule-1 (ICAM-1). Although ICAM-1 expression is regulated by NF-kappaB, recent studies have suggested that additional signaling mechanisms may also be involved. The goal of this study was to determine whether mitogen-activated protein (MAP) kinases, including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAP kinase (p38), mediate thrombin-induced ICAM-1 expression in endothelial cells. METHODS: Western blot analysis using anti-ICAM-1 antibody and luciferase assays were performed in cultured endothelial cells after addition of signal transduction inhibitors or transfection of various gene constructs. JNK kinase activity was determined by a kinase assay using c-Jun as a substrate or by Western blot analysis with anti-phospho-JNK antibody. RESULTS: Treatment of endothelial cells with the JNK-specific inhibitors, SP600125 or JNK inhibitory peptide 1 (JNKI1), resulted in a significant decrease in thrombin-induced ICAM-1 expression as demonstrated by Western blot analysis (67 +/- 3% and 72 +/- 7%, respectively). In contrast, inhibitors of MEK and p38 had only minimal effect. The combination of SP600125 and the NF-kappaB inhibitor, BAY11-7082, resulted in complete inhibition of thrombin-induced ICAM-1 expression. The Galpha(q) inhibitor, YM-254890, inhibited thrombin-induced JNK activation and ICAM-1 expression. Dominant-negative Ras and Rac1, but not Rho, inhibited thrombin-induced JNK activation and ICAM-1 promoter activity. Finally, thrombin-induced JNK activation and ICAM-1 promoter activity were inhibited by betaARK1ct (a Gbetagamma subunit scavenger) and Csk. CONCLUSIONS: These data suggest that, in concert with NF-kappaB, JNK regulates thrombin-induced ICAM-1 expression by a mechanism that is dependent on Galpha(q), Gbetagamma, Ras, Rac1 and the Src kinase family.

Animals↗

PubMed2005

Allele-specific transcript quantification detects haplotypic variation in the levels of the SDF-1 transcripts.

It has been suggested that SDF1-G801A, a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the SDF1 gene, is associated with susceptibility to diseases such as AIDS and type-I diabetes. However, experimental studies examining the effect of SDF1-G801A on SDF-1 expression have not supported its functional importance. In this study, to examine whether other polymorphisms have a cis-acting effect on SDF1 expression, we carried out haplotype analyses of the SDF1 gene and the allele-specific transcript quantification utilizing Epstein-Barr virus-transformed lymphoblastoid cell lines with heterozygous genotype for SDF1-G801A. Haplotype-based analyses on the proportion of the allele-specific transcripts revealed the presence of haplotypes associated with a decreased amount of the transcripts. In addition, we observed haplotypic variation in response to dibutyl cyclic AMP and tetradecanoyl phorbol acetate that enhances the levels of SDF-1 transcripts probably through activation of transcription factors. Showing evidence that polymorphisms other than the SDF1-G801A have a cis-acting effect on expression of SDF-1 transcripts, the results of this study contribute to the interpretation of previous disease-association studies and to the selection of SNP markers for future studies. As shown in this study, allele-specific transcript quantification coupled with haplotype analyses can be an effective tool for detecting cis-acting polymorphisms in expressional regulation.

Alleles↗

PubMed2005

Recent origin and cultural reversion of a hunter-gatherer group.

Contemporary hunter-gatherer groups are often thought to serve as models of an ancient lifestyle that was typical of human populations prior to the development of agriculture. Patterns of genetic variation in hunter-gatherer groups such as the Kung and African Pygmies are consistent with this view, as they exhibit low genetic diversity coupled with high frequencies of divergent mtDNA types not found in surrounding agricultural groups, suggesting long-term isolation and small population sizes. We report here genetic evidence concerning the origins of the Mlabri, an enigmatic hunter-gatherer group from northern Thailand. The Mlabri have no mtDNA diversity, and the genetic diversity at Y-chromosome and autosomal loci are also extraordinarily reduced in the Mlabri. Genetic, linguistic, and cultural data all suggest that the Mlabri were recently founded, 500-800 y ago, from a very small number of individuals. Moreover, the Mlabri appear to have originated from an agricultural group and then adopted a hunting-gathering subsistence mode. This example of cultural reversion from agriculture to a hunting-gathering lifestyle indicates that contemporary hunter-gatherer groups do not necessarily reflect a pre-agricultural lifestyle.

Chromosomes, Human, Y↗

PubMed2005

Promoter analysis and aberrant expression of the MUC5B gene in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a chronic inflammatory airway disease predominantly affecting Asian populations. DPB is considered to be a complex genetic disease. Considering the mucous hypersecretion of the disease, we hypothesized that the transcriptional activity of mucin genes may be altered in DPB. We analyzed nucleotide sequences of regulatory region of six mucin genes--MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7--and detected their promoter polymorphisms. Among them, the insertion/deletion polymorphism identified in the MUC5B gene was significantly associated with the disease (p = 0.0001). Transcriptional activity observed in the three major promoter haplotypes corresponded to the strength of the disease association in which these haplotypes are involved. Immunohistochemistry of the lung tissues of DPB revealed that MUC5B was abundantly expressed not only in bronchial glands but also in increased numbers of goblet cells on the bronchial surface, where MUC5AC is predominant and MUC5B expression is generally scarce in the normal lung. Marked mucous hypersecretion observed in DPB may be partly explained by increased and aberrant expression of MUC5B. The possible involvement of MUC5B gene in DPB was demonstrated. A further role of the MUC5B polymorphism in its pathogenesis should be studied in the future.

Aged↗

PubMed2005

Phylogenetic heterogeneity of new HTLV type 1 isolates from southern India in subgroup A.

Seven isolates of human T cell leukemia virus type 1 (HTLV-1) were taken in southern India and phylogenetically analyzed to gain new insights into the origin and dissemination of HTLV-1 in the subcontinent. The new Indian HTLV-1s were found to be members of subgroup A (Transcontinental subgroup) of the Cosmopolitan group. They formed three different clusters (South African/Caribbean, Middle Eastern, and East Asian clusters). These results demonstrate that Indian HTLV-1s are genetically heterogeneous and include the most divergent strain of subgroup A. On the basis of these results, we speculate that subgroup A HTLV- 1s may have been present for thousands of years in India.

Adult↗

PubMed2005

Human papillomavirus genotypes and the p53 codon 72 polymorphism in cervical cancer of Northeastern Thailand.

Human papillomavirus (HPV) infection including sub-strain identification was studied in patients with squamous cell cervical cancer (SCCA) in Northeastern Thailand. Subjects were 90 cases of SCCA and 100 healthy controls. Prevalence of high-risk group of HPV infection in the controls and the SCCA patients were 13.0% and 86.7%, respectively. The HPV infection significantly increased the risk for cervical cancer 43.5-fold (95% confidential interval: 17.5-110.6; P <0.00001). Among HPV carrier patients with SCCA (n = 78), HPV-16 was also prominent (70.5%) followed by HPV-18 (23.1%). There was no statistical difference in the subtype distribution between the SCCA and the control groups. There was no significant association between genotype distribution of the p53 codon 72 polymorphism and HPV infection. HPV infection was confirmed as a critical risk factor for cervical cancer development in Northeast Thailand. Since polymorphism of the p53 itself as well as in combination with HPV infection may not be a genetic risk for cervical cancer, much attention should be paid to other risk factors such as sexual behavior and smoking.

Carcinoma, Squamous Cell↗