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Biomedical subjects

N Mizuki

Publications and source records attributed to N Mizuki.

At least 55 records · Page 3Linked to original sources
PubMed1997

Mouth and genital ulcers with inflamed cartilage (MAGIC syndrome): a case report and literature review.

A 39-year-old woman had relapsing polychondritis and Behçet's disease, which was described as mouth and genital ulcers with inflamed cartilage syndrome (MAGIC). Serologic human leukocyte antigen analysis showed A24 (9), A31 (19), B56 (22), B62 (15), Cw6, DR4, DR9. Human leukocyte antigen allele analysis revealed DRB1* 0406/0901, DQA1* 0301/0301, DQB1* 0302/0303, DPB1* 0201/0501 through determining the genotype using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Treatment with methotrexate (5 mg/week) and pentoxifylline (300 mg/d) was effective to control oral ulcers, erythema nodosum, and arthritis.

Adult↗
PubMed1997

Analysis of allelic variation of the TAP2 gene in sarcoidosis.

Sarcoidosis is a systemic granulomatous disease and the DRB1 gene of the DR subregion has been implicated for determining the genetic susceptibility to the disease. We evaluated the allelic variation of the TAP2 gene using the PCR-RFLP method as well as the mismatched PCR-RFLP method in 82 Japanese patients with sarcoidosis and 92 healthy controls. A new allele, TAP2*0103 and a new polymorphic variation at codon 577 in addition to TAP2*0101, TAP2*0102 and TAP2*0201 have been recognized in the Japanese subjects. No significant differences were observed in the frequencies of any TAP2 alleles or dimorphism at codon 577 between the patients and healthy controls. Polymorphic variation of the TAP2 gene does not confer the susceptibility to sarcoidosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
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

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

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↗
PubMed1996

HLA-C genotyping of patient with Behçet's disease in the Japanese population.

Behçet's disease has been known to be strongly associated with a particular HLA-B allele, B51. To address the possibility that the HLA-C gene, which is closely linked to HLA-B but has been poorly defined for allo-antigen specificity by the serologic method is involved in the susceptibility to Behçet's disease, HLA-C genotyping was performed for 90 Japanese Behçet's disease patients by the PCR-SSP method. The frequencies of HLA-Cw*14 and -Cw*15 were significantly higher in the patient with Behçet's disease as compared to the controls (48.9% vs. 24.0%, p = 0.0005, and 17.8% vs. 7.3%, p = 0.0434, respectively). On the other hand, the frequencies of HLA-Cw*0304 and -Cw*01 were significantly decreased in the patient group as compared to the control group (7.8% vs. 25.0%, p = 0.0027, and 23.3% vs. 37.5%, p = 0.0398, respectively). The significantly higher HLA-Cw*14 and -Cw*15 alleles may tightly correlate with the B51 antigen, and hence may have increased as a result of a linkage disequilibrium with B51. Accordingly, the HLA-C allele frequencies were compared for the B51-positive or -negative patients and controls, but there was no HLA-C allele showing a significant difference between these patient and control groups. Conversely, analysis of the HLA-B allelic distribution in association with HLA-Cw*14 revealed that in the healthy controls, B44 and B51 were present at the frequencies of 57.1% and 35.7% of the HLC-Cw*14-positive individuals, respectively. In contrast, in the Cw*14-positive patients the frequency of B44 was merely 14.0% (p = 0.0001) and that of B51 was significantly high, amounting to 82.0% (p = 0.0001). These facts suggest that the pathogenic gene of Behçet's disease is not the HLA-C gene (HLA-Cw*14 and/or HLA-Cw*15) but the HLA-B gene (HLA-B51) itself or a non-HLA gene residing in the centromeric side of the HLA-B gene rather than in the telomeric side around the HLA-C gene. This finding supports our previous mapping result, which located the susceptible gene between the TNF and HLA-B genes.

Alleles↗
PubMed1996

Analysis of HLA-DM polymorphisms in sarcoidosis.

Sarcoidosis is a multisystemic granulomatous disorder showing significant increases in the HLA-DRB1*11, *12, *14 and *08 alleles in the Japanese population. To evaluate the role of polymorphism in the DMA and DMB genes in predisposition to sarcoidosis, seventy Japanese patients with sarcoidosis and 95 unrelated healthy controls were analyzed in the third exon polymorphisms within the DMA and DMB genes by the PCR-RFLP method. There were no differences in the distribution of DMA alleles between the patient and control groups. The frequency of DMB*0102 was higher (p < 0.05) and that of DMB*0101 was lower (p < 0.05) in the patients than in the healthy controls. However, this association and negative association could be explained by linkage disequilibrium with the disease-associated DRB1 alleles. The DMA and DMB genes do not primarily confer the susceptibility to sarcoidosis.

Adult↗
PubMed1996

Isolation of cDNA and genomic clones of a human Ras-related GTP-binding protein gene and its chromosomal localization to the long arm of chromosome 7, 7q36.

A Ras-related GTP-binding protein cDNA has been isolated from a human skin fibroblast cDNA library using a genomic subclone derived from a YAC clone as a probe. The polypeptide, consisting of 184 amino acids deduced from nucleotide sequences, contains five repeats of the Ras-related GTP-binding region and is highly homologous to the rat RHEB (Ras homologue enriched in brain) gene, which encodes a Ras-related growth factor- and synaptic activity-regulated protein, with 98.9% amino acid identity. Therefore, it is suggested to be a human homologue of the rat RHEB protein, and we have designated it human RHEB. Using fluorescence in situ hybridization, we concluded that this human RHEB gene was localized to band q36 on chromosome 7. Considering the chromosomal localization as well as the potential function of this protein, it will be very important to investigate whether it may play a role in the etiopathogenesis of holoprosencephaly type 3 or hereditary sacral agenesis, in which the disease susceptible locus is linked to the microsatellite marker, D7S22, in this chromosomal region, 7q36.

Amino Acid Sequence↗
PubMed1996

Allelic repertoire of the human MHC class I MICA gene.

The hallmark of the classical major histocompatibility complex (MHC) class I molecules is their astonishing level of polymorphism, a characteristic not shared by the nonclassical MHC class I genes. A distinct family of MHC class I genes has been recently identified within the human MHC class I region. The MICA (MHC class I chain-related A) gene in this family is a highly divergent member of the MHC class I family and has a unique pattern of tissue expression. We have sequenced exons encoding the extracellular alpha1, alpha2, and alpha3 domains of the MICA gene from twenty HLA homozygous typing cell lines and four unrelated individuals. We report the identification of eleven new alleles defined by a total of twenty-two amino acid substitutions. Thus, the total number of MICA alleles is sixteen. Interestingly, a tentative superimposition of MICA variable residues on the HLA-A2 structure reveals a unique pattern of distribution, concentrated primarily on the outer edge of the MICA putative antigen binding cleft, apparently bordering an invariant ligand binding site.

Alleles↗
PubMed1996

Genetic polymorphisms of the major histocompatibility complex-encoded antigen-processing genes TAP and LMP in sarcoidosis.

Sarcoidosis is a granulomatous disease showing a significant increase in the HLA-DR5, -DR6, and -DR8 associated alleles in Japanese. To investigate whether the class I antigen-processing genes, encoded within the MHC class II region between the HLA-DP and -DQ loci, are involved in determining the susceptibility to sarcoidosis, TAP1, TAP2, and LMP2 alleles were analyzed by the PCR-RFLP method in 85 Japanese patients with sarcoidosis and 91 healthy controls. There were no significant differences in the distribution of TAP1 and LMP2 alleles between the subgroups of the patients and controls positive or negative for DR5, DR6, and DR8. A significant decrease in the frequency of TAP2*0201 was found among the patients negative for DR5, DR6, and DR8 as compared to the DR-matched controls (p < 0.05), but this could be explained by its linkage disequilibrium to the negatively associated allele DR1. These findings suggest that the TAP or LMP2 gene is not primarily involved in the susceptibility to sarcoidosis. In the course of this study, a linkage disequilibrium was observed in the Japanese population between TAP1 and TAP2 alleles, TAP1*0201 and TAP2*0102.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

LMP7 polymorphism in Japanese patients with sarcoidosis and Behçet's disease.

To evaluate the influence of the MHC-linked LMP7 gene on disease susceptibility in HLA class I and class II-associated diseases, the distribution of LMP7 alleles was determined using the PCR-RFLP method in 69 Japanese patients with Behçet's disease, 65 patients with sarcoidosis, and 100 unrelated healthy controls. No differences were found between either of the patient groups and the healthy control group, indicating that LMP7 allelic variation may not contribute to the pathogenesis of either Behçet's disease or sarcoidosis. We also analyzed linkage disequilibria between LMP7 and HLA class II alleles in Japanese populations.

Alleles↗
PubMed1996

Genetic polymorphisms in the keratin-like S gene within the human major histocompatibility complex and association analysis on the susceptibility to psoriasis vulgaris.

Psoriasis vulgaris is associated with the HLA-Cw6 and Cw7 antigens. However, it has not yet been clarified if the HLA-Cw6 and Cw7 genes themselves are the susceptible gene related to this disease or if it is some other non-HLA gene in a linkage disequilibrium with these HLA-C alleles. The S gene, recently identified in the HLA class I region 160 kb telomeric of HLA-C, encodes a keratin-like protein and is expressed specifically in the granular layer of the epidermis. Therefore, it is tempting to speculate that the S gene is one of the strong candidate genes responsible for the pathogenesis of psoriasis vulgaris. Direct sequencing of the first and second exon of the S gene after polymerase chain reaction (PCR) amplification has allowed the identification of two diallelic polymorphic sites in exon I and seven diallelic polymorphic sites in exon 2, three among which result in amino acid exchanges, a Ser-Phe substitution at amino acid position 186, a Gly-Val substitution at position 393 and a Ser-Leu substitution at position 394. No significant difference in the dimorphic distributions of the S gene was observed between the patients with psoriasis vulgaris and healthy controls, suggesting that the susceptible gene for psoriasis is not the S gene itself.

Disease Susceptibility↗