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H Inoko

Publications and source records attributed to H Inoko.

At least 163 records · Page 9Linked to original sources
PubMed1997

Trinucleotide repeat polymorphism within exon 5 of the MICA gene (MHC class I chain-related gene A): allele frequency data in the nine population groups Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian.

We recently identified a trinucleotide repeat polymorphism, (GCT)n, within the transmembrane (TM) segment of the human MHC class I MICA gene (MHC class I chain-related gene A). Five distinct alleles (A4, A5, A5.1, A6, A9) corresponding to 4, 5, 5 with one nucleotide insertion, 6 and 9 repetitions, respectively, have been detected in various HLA-homozygous B cell lines. Here we present allele frequencies for this trimeric short tandem repeat (STR) in 604 unrelated individuals collected from nine human populations (Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian) determined using the polymerase chain reaction (PCR) combined with fluorescent-based automated fragment detection technology. All alleles were present in each population, but allelic distributions varied from one population to another. No new alleles (such as A7 or A8) were identified. The evolutionary and structural significance of these data as well as the potential application to forensic medicine is discussed.

Alleles↗
PubMed1997

Molecular genetic analysis of HLA class II alleles in Japanese patients with melanoma.

Distribution of HLA-DQA, -DQB and -DPB alleles in ninety-six Japanese patients with melanoma was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the association between clinical parameters and the presence of certain HLA class II alleles investigated. The frequency of HLA-DQB1*0302 was increased, while those of DQA1*0101(04), -DQA1*0401 and DRB1*0802 were decreased in melanoma patients compared with controls. Moreover, the frequency of HLA-DQA1*0103 in patients with acral lentiginous melanoma was increased compared with controls. However, none of these HLA class II alleles showed significant positive or negative associations after correction of the P value. In addition, there was no correlation between these antigens and clinical parameters. These results indicate that HLA class II alleles may not contribute to a strong susceptibility to melanoma in the Japanese.

Adult↗
PubMed1997

MICA gene and ankylosing spondylitis: linkage analysis via a transmembrane-encoded triplet repeat polymorphism.

In order to address the possibility that the MICA gene located 47 kb upstream from HLA-B is involved in the pathogenesis of ankylosing spondylitis (AS), we have investigated microsatellite polymorphism in the transmembrane region of MICA in Caucasian patients with AS. The microsatellite allele consisting of 4 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc<0.0000001) than in the ethnically matched control group. However, the frequency of the (GCT/AGC)4 allele was significantly low in the B27-positive patients than in the B27-positive healthy controls (Pc=0.0145). These observations suggest that B27 itself remains the primary genetic marker for AS, although the significantly dissimilar phenotype frequency of the (GCT/AGC)4 allele in B27-positive patients and healthy individuals may reflect the existence of other genetic factor(s) in the HLA-B27 haplotype involved in the development of AS.

Alleles↗
PubMed1997

Identification of a novel HLA-B allele (B*4202) in a Saudi Arabian family with Behçet's disease.

A new HLA-B antigen, tentatively called HLA-B42AND, was identified as a B42 serologic variant in a Saudi Arabian family. DNA sequencing analysis of the second and third exon of this new B allele revealed that B42AND was identical to B*4201 except for a single T to C substitution at position 97 of exon 2. This substitution results in histidine (CAC) at codon 9 in B42AND instead of tyrosine (TAC) in B*4201. The antigen frequency of B42AND in a Saudi Arabian population was around 10%. This novel B42AND has officially been named HLA-B*4202.

Alleles↗
PubMed1997

A strong association between HLA-B*5101 and Behçet's disease in Greek patients.

Behçet's disease is known to be associated with HLA-B51, one of the split antigens of HLA-B5, among many different ethnic groups. In a Greek population, an increased incidence of HLA-B5 in the patient group has also been reported. Because the B51 antigen has been recently identified to comprise seven alleles, B*5101-B*5107, we performed HLA-B51 allele genotyping by the PCR-SSP method as well as serological HLA-A and -B typing among 31 Greek patients with Behçet's disease to investigate whether there is any correlation between one particular B51-associated allele and Behçet's disease. The frequency of B51 was remarkably high (80.6%) in the patient group as compared to the ethnically matched control group (26.7%). In addition, HLA-A26 was also increased in the patients (29.0%) as compared with the healthy controls (3.3%). B51 allele genotyping revealed that all these B51-positive patients carried B*5101. This study revealed a strong association of Behçet's disease in Greeks with one of the B51 subantigens, providing insight into the molecular mechanism underlying an HLA association with Behçet's disease.

Behcet Syndrome↗
PubMed1997

Triplet repeat polymorphism in the NOTCH4 gene with the human major histocompatibility complex in a healthy population and patients with a salivary gland tumor in Japan.

The NOTCH4 gene, the human counterpart of the mouse mammary tumor gene, int-3, has been recently localized near the boundary of the HLA class II and class III regions. This gene is one of candidates for development of salivary gland tumor. Microsatellite polymorphism of (CTG)n repeat in the signal peptide domain of NOTCH4 was analyzed in Japanese including the patients with salivary gland tumor. Four alleles consisting of 6, 9, 10 and 11 repetitions of CTG (Leu) were observed and found to be in linkage disequilibria with HLA class I and class II alleles. No significant association of this microsatellite polymorphism with the disease were observed in 26 samples of salivary gland tumor. In this neoplasia, neither large-scale deletion nor translocation was detected around the NOTCH4 gene using genomic Southern hybridization analysis by the NOTCH4 cDNA as a probe.

Alleles↗
PubMed1997

Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation.

Plasma levels of tumor necrosis factor (TNF) alpha are raised during acute rejection following organ transplantation. Variations in TNF alpha production have been found to be associated with the polymorphism of TNF microsatellite. Therefore, there is a possibility that a transplant recipient with some type of TNF microsatellite can be a high-risk patient of graft rejection. The purpose of this study was to examine whether TNF microsatellite polymorphism is related to acute allograft rejection. We investigated the relation of two microsatellites, TNFa and TNFd, to acute rejection after renal transplantation. Among 189 primary living-related renal transplantations from one haplotype-mismatched and one DRB1-mismatched donor, we analyzed TNF microsatellites of 163 patients whose DNA were available to this study. The frequency of the TNFa9 microsatellite allele was significantly higher in the rejection group compared to the rejection-free group. In contrast, the frequency of TNFd4 was significantly lower in the rejection group compared to the rejection-free group. TNFa9 and TNFd4 showed strong associations with HLA-B35 and B44, respectively. However, the TNF microsatellite locus was more closely related to acute rejection than HLA-B. It was suggested that the analysis of TNF microsatellite polymorphism can provide useful information in predicting prognosis after transplantation.

Biomarkers↗
PubMed1997

Molecular genetic studies on DNA polymorphism of the HLA class II genes associated with human longevity.

Okinawan Japanese are well known for their longevity; the population rate of centenarians in Okinawa is about 3.8 times higher than that of the whole Japan, where the average life expectancies both among men and among women are the highest in the world. In this study, we analyzed HLA class II alleles of Okinawan centenarians by the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method for the purpose of clarifying the presence of primary genetic factors in the major histocompatibility complex (MHC) region associated with human longevity. DRB1*1401, DQB1*0503, DQA1*0101=0104 and DQA1*05 were significantly increased in the centenarians. The significant increase of HLA-DQB1*0503 and/or DQA1*0101=0104 in the centenarians can be explained by a linkage disequilibrium with DRB1*1401, or vice versa. Further, the tendency was observed toward increase with respect to DRB1*0101 and DRB1*1201. These data suggest that several alleles of the HLA-DRB1 and/or HLA-DQ genes are involved in human longevity.

Adult↗
PubMed1997

Major histocompatibility complex class II alleles in Kazak and Han populations in the Silk Route of northwestern China.

Genetic polymorphism of the HLA class II loci including the DRB1, DQA1, DQB1 and DPB1 genes was investigated by the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method in a Kazak population inhabiting the most northwestern part of China, Urümqi in the Xinjiang Uygur Zizhiqu as well as in a Han population in the same area. Forty-two Kazak and 59 Han unrelated volunteers were enrolled in this study. Among 51 DRB1 alleles tested, 29 alleles were detected, and DRB1*0301 (13.1%) and DRB1*07 (10.7%) in Kazak and DRB1*0901 (11.9%), DRB1*1501 (11.0%) and DRB1*07 (11.0%) in northwestern Han were highly predominant. In 8 DQA1 alleles detected, DQA1*0501 (29.8%) and DQA1*0301 (23.8%) in Kazak, and DQA1*0301 (28.8%) and DQA1*0102 (19.5%) in northwestern Han were the most and the second most common alleles, respectively. Of 18 DQB1 alleles tested, 14 were observed, among which DQB1*0201 and DQB1*0301 were very frequent both in Kazak (23.8% and 21.4%, respectively) and northwestern Han (18.6% and 16.9%, respectively) populations. Of 37 DPB1 alleles tested, 14 were detected. Among them, the frequencies of DPB1*0401 (21.4%), DPB1*0501 (20.2%), DPB1*0402 (19.0%) and DPB1*0201 (16.7%) in Kazak, and those of DPB1*0501 (38.1%) and DPB1*0201 (16.1%) in northwestern Han were highly increased. Several three-locus haplotypes were recognized to predominate significantly, namely DRB1*0301-DQA1*0501-DQB1*0201 (13.1%) and DRB1*0701-DQA1*0201-DQB1*0201 (8.3%) in Kazak; and DRB1*0901-DQA1*0301-DQB1*0303 (11.9%) and DRB1*0701-DQA1*0201-DQB1*0201 (10.2%) in northwestern Han. The dendrogram constructed by the neighbor-joining (NJ) method based on the allele frequencies of the DRB1, DQA1, DQB1 and DPB1 genes of 12 representative populations all over the world including northern Han, southern Han, Manchu and Japanese suggested that Kazak and northwestern Han were the closest to each other, but Kazak was a little farther from the Asian ethnic groups than northwestern Han.

Alleles↗
PubMed1997

Complete HLA-A DNA typing using the PCR-RFLP method combined with allele group- and sequence-specific amplification.

We have established a practical method of complete high-resolution typing for all HLA-A alleles using the polymerase chain reaction (PCR)-restriction fragment-length polymorphism (RFLP) technique combined with allele group- and sequence-specific amplification. The second and third exons of the HLA-A gene, in which most allelic variations are observed, were separately amplified by PCRs with 3 and 4 group-specific primer pairs, respectively. Each PCR-amplified product was digested by allele-specific restriction endonucleases and then subjected to electrophoresis on a 10% polyacrylamide gel. In this way, 62 out of 79 HLA-A alleles could be discriminated by the RFLP patterns derived from the genetic polymorphism in the exon 2 and 3 domains. The remaining 17 alleles could be defined unequivocally by either PCR-RFLP analysis after exon 4 amplification or PCR analysis with sequence-specific primers (SSP). By this method, complete HELA-A genotyping for all homozygous and heterozygous combinations can be accomplished, establishing technically simple, economical and practical routine typing of the HLA-A gene, especially for small samples.

Alleles↗
PubMed1997

Triplet repeat polymorphism within the NOTCH4 gene located near the junction of the HLA class II and class III regions in narcolepsy.

A polymorphic (CTG)n microsatellite repeat was found in the signal peptide domain of the NOTCH4 gene located near the junction of the class II and class III regions of the human major histocompatibility complex. This gene belongs to a multigene family of NOTCH originally identified as a differential factor of neuronal cells. To ascertain whether the NOTCH4 gene is involved in the development of neurogenic disease, narcolepsy, which is known to be tightly associated with HLA-DR15, this microsatellite polymorphism of the (CTG)n repeat was analyzed in Japanese patients with narcolepsy One allele, 9 repetitions of CTG (Leu) was significantly increased in the patient group. However, the significant increase of this allele in the patient group could be explained by a strong linkage disequilibrium with the HLA class II alleles, DRB1*1501, DQA1*0102 and DQB1*0602, which were more strongly associated with the disease. These results suggest that the (CTG)n repeat polymorphism in NOTCH4 does not primarily determine the susceptibility to narcolepsy.

Alleles↗
PubMed1997

Genetic polymorphism in intron 6 of the LMP7 gene in Japanese and its association with sarcoidosis.

Genetic polymorphism in intron 6 of the LMP7 gene was investigated using polymerase chain reaction-restriction fragment length polymorphism in 90 unrelated healthy Japanese controls and 66 Japanese patients with sarcoidosis. Four alleles, including two new ones recently identified in Koreans, LMP7*C and LMP7*D, were found in the Japanese population. The frequency of LMP7*C in the sarcoidosis patients was higher than in the healthy controls. However, this difference might be explained by a secondary association with HLA-DRB1*08 in the HLA-DRB1 gene, which is thought to be the gene primarily responsible for susceptibility to sarcoidosis.

Alleles↗
PubMed1997

Precise switching of DNA replication timing in the GC content transition area in the human major histocompatibility complex.

The human genome is composed of long-range G+C% (GC%) mosaic structures thought to be related to chromosome bands. We previously reported a boundary of megabase-sized GC% mosaic domains at the junction area between major histocompatibility complex (MHC) classes II and III, proposing it as a possible chromosome band boundary. DNA replication timing during the S phase is known to be correlated cytogenetically with chromosome band zones, and thus the band boundaries have been predicted to contain a switch point for DNA replication timing. In this study, to identify to the nucleotide sequence level the replication switch point during the S phase, we determined the precise DNA replication timing for MHC classes II and III, focusing on the junction area. To do this, we used PCR-based quantitation of nascent DNA obtained from synchronized human myeloid leukemia HL60 cells. The replication timing changed precisely in the boundary region with a 2-h difference between the two sides, supporting the prediction that this region may be a chromosome band boundary. We supposed that replication fork movement terminates (pauses) or significantly slows in the switch region, which contains dense Alu clusters; polypurine/polypyrimidine tracts; di-, tri-, or tetranucleotide repeats; and medium-reiteration-frequency sequences. Because the nascent DNA in the switch region was recovered at low efficiency, we investigated whether this region is associated with the nuclear scaffold and found three scaffold-associated regions in and around the switch region.

Base Sequence↗
PubMed1997

Pathogenic gene responsible for the predisposition of Behçet's disease.

HLA-B51 is well known to be associated with Behçet's disease (BD) in many different ethnic groups. The hypothesis may be presented that B51 molecules are primarily involved in BD development through specific antigen presentation. Furthermore, HLA-C genotyping by the polymerase chain reaction-sequence specific primers method suggests that the BD pathogenic gene is not the HLA-C gene itself but some other gene located near the HLA-B gene. Polymorphic analysis of the Tau-a microsatellite between the HLA-B and TNF genes indicates that the pathogenic gene of BD is not the HLA-B51 gene itself but other gene located around the HLA-B gene. Recent studies suggest that many novel genes exist in the region between the TNF and HLA-B or HLA-C genes such as MIC and PERB, etc. and furthermore, many unidentified new genes have been suggested to exist in this region. In this paper, the present situation of the investigations on the genetic predisposition responsible for BD was reviewed.

Animals↗
PubMed1997

Molecular genetics (HLA) of Behçet's disease.

Behçet's disease (BD) has been known to be strongly associated with the human leukocyte antigen (HLA) B51. This B51 association has been confirmed in many different ethnic groups between the Middle East and Japan, and it has been proposed that BD is prevalent in those ethnic groups along the old Silk Route. The hypothesis could be made that B51 molecules are primarily involved in BD development through specific antigen presentation. However, polymorphic analyses of the TNFB gene and Tau-a microsatellite between the HLA-B and TNF genes indicate that the pathogenic gene of BD is not the HLA-B51 gene itself but another gene located around the HLA-B gene. HLA-C genotyping by the PCR-SSP method also suggests that the BD pathogenic gene is not the HLA-C gene itself but other gene located near the HLA-B gene. Recently we sequenced a single contig of 236,822 bp from the MICA gene (58.2 kb centromeric of HLA-B) to 90.8 kb telomeric of HLA-C and identified 8 novel genes designated NOB1-8 (NOB: new organization associated with HLA-B). During the course of the genomic sequence analysis we clarified the genetic structure of the MICA (MHC class I chain-related gene A) gene and found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmebrane (TM) region. Furthermore, the microsatellite allele consisting of 6 repetitions of GCT/AGC (MICA A6 allele) was present at a significantly higher frequency in the BD patient group than in the control group and a significant fraction of B51-negative patients were positive for this MICA A6 allele. These results suggest the possibility of a primary association of BD with MICA rather than HLA-B.

Animals↗