SEARCH · PubMed Health

Results for “HLA polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,387 records · Page 77Linked to original sources

PubMed2005

Single nucleotide polymorphisms in the regulatory regions of the HLA-DRB-expressed genes.

DRB genes encode proteins that play an important role in the immune response, and their expressional regulation is crucial to the immune reaction. Sequence variation at the regulatory region can directly affect the gene expression level. The aim of the present study was to use Chinese samples to investigate the variation in the regulation region of the human leukocyte antigen (HLA)-DRB-expressed genes. Seventy- one single nucleotide polymorphisms (SNPs) were found in the four HLA-DRB-expressed genes. By comparing these data with SNPs in the U.S. National Center for Biotechnology Information dbSNP database, 69 SNPs (97.2%) were found to be novel. In addition, two genetic variations of insertion-deletion polymorphisms were discovered within the regulatory region of HLA-DRB1 gene. These polymorphisms can be used as resources of markers for association studies of complex diseases, for assessment of individual predisposition to diseases, and as research markers for population genetics and evolution.

Base Sequence↗

PubMed1997

HLA-B27 presents a peptide from a polymorphic region of its own molecule with homology to proteins from arthritogenic bacteria.

A possible mechanism for the pathogenesis of HLA-B27-associated spondyloarthropathies is that peptides from arthritogenic bacteria with homology to endogenous self-peptides presented by HLA-B27, including those derived from HLA-B27 itself, could elicit an autoimmune T-cell response upon infection. We report here that an undecamer corresponding to the polymorphic region of HLA-B27 spanning residues 169-179 is presented in vivo by the B*2701, B*2704 and B*2706 subtypes, but was not detected in the B*2703-bound peptide pool. This peptide binds to B*2705 in vitro with sufficient affinity to allow its natural presentation by this subtype, but it binds with low affinity to B*2703. In spite of homology of this peptide to proteins from arthritogenic bacteria, its binding specificity does not correlate with current evidence concerning association of HLA-B27 subtypes to ankylosing spondylitis, suggesting that presentation of this peptide is not the critical feature that determines linkage of HLA-B27 to this disease.

Animals↗

PubMed1997

Identification of HLA-C alleles using PCR-single-strand-conformation polymorphism and direct sequencing.

Alleles encoding HLA-C antigens in Japanese were identified by polymerase chain reaction followed by single strand conformation polymorphism (PCR-SSCP) and nucleotide sequencing analyses. The results showed that at least sixteen different alleles code for eight serologically detectable antigen groups and undetectable blanks. Cw1 was mainly encoded by Cw*0102, whereas two split antigens of Cw3, Cw9 and Cw10, were encoded by Cw*0303 and Cw*0304, respectively. Cw4 and Cw6 were encoded by Cw*0401 and Cw*0602, respectively. Seven alleles, Cw*0801, Cw*0803, Cw*1202, Cw*1203, Cw*1402, Cw*1403 and Cw*1502, were found to encode serological HLA-C "blanks" in Japanese. Moreover, errors in the published nucleotide sequences of Cw*0501 and Cw*1201 were corrected. Twenty-one HLA-C alleles were distinguished from each other by means of group-specific PCR amplification followed by the SSCP method developed in the present study. The system using genomic DNAs can be used effectively for identification of new HLA-C alleles.

Alleles↗

PubMed1997

Polymorphism of conventional genetic markers and HLA system in Turkey.

This study is part of a general survey in which the regional variability of various genetic markers in Turkey will be analyzed with special regard to its application in forensic medicine. Blood samples from 3173 unrelated healthy individuals of both sexes and from different regions of Turkey have been sampled and were typed for the blood group polymorphisms AB0, MNSs, Kell, Duffy, Kidd, P, Lutheran and Lewis, for the red cell enzyme polymorphisms adenylate kinase (AK), glyoxalase (GLO), phosphoglucomutase (PGM), esterase D (ESD), red cell acid phosphatase (aP), and for the serum protein polymorphisms group specific component (vitamin D binding protein, GC) and transferrin (TF). In addition to this the HLA-A and HLA-B antigens of the major histocompatibility complex (HLA) were also typed in 973 individuals. The blood group polymorphisms were typed by the classical haemagglutination methods. Serum protein and red cell enzyme polymorphisms were determined by conventional cellulose acetate electrophoresis. HLA antigens were typed by the standard two stage microlymphocytotoxicity technique. Genetic equilibrium can be assumed for all polymorphic systems under study. The results indicate some regional differences in the distribution of allele frequencies.

Adolescent↗

PubMed2002

Genetic analysis of multicase families of visceral leishmaniasis in northeastern Brazil: no major role for class II or class III regions of HLA.

Familial aggregation, high relative risk to siblings, and segregation analysis, suggest genetic control of visceral leishmaniasis in Brazil. Class II gene effects in mice, and high circulating tumour necrosis factor alpha in humans, provide reasons to target HLA. Fifteen polymorphic markers across 1.03 Mb (DQB1 to TNFa) were genotyped (87 multicase families; 638 individuals). Model-based parametric analyses using single-point combined segregation and linkage in COMDS, or multi-point linkage in ALLEGRO, failed to detect linkage. Model-free nonparametric affected sibling pair (SPLINK) or NPL(all) score (ALLEGRO) analyses also failed to detect linkage. Information content mapping confirmed sufficient marker information to detect linkage. Analysis of simulated data sets demonstrated that these families had 100% power to detect NPL(all) scores of 5 to 6 (>LOD4; P < 0.00001) over the range (7% to 61%) of age-related penetrances for a disease susceptibility gene. The extended transmission disequilibrium test (TDT) showed no consistent allelic associations between disease and the 15 loci. TDT also failed to detect significant associations between extended haplotypes and disease, consistent with failure to detect significant linkage disequilibrium across the region. Linkage disequilibrium between adjacent groups of markers (HLADQ/DR; 82-1/82-3/-238bpTNFA; LTA/62/TNFa) was not accompanied by significant global haplotype TDT associations with disease. The data suggest that class II/III regions of HLA do not contain major disease gene(s) for visceral leishmaniasis in Brazil.

Animals↗

PubMed1984

Confirmation of F13A assignment and sequence information concerning F13A-HLA-GLO.

The polymorphism of the blood clotting factor F13A was examined in some of our Danish material of normal families. A total of four alleles were recognized, with allele frequencies as follows: F13A *1 = 0.817, F13A *2 = 0.177, F13A *4 = 0.003 and a new allele F13A *5 = 0.003. The distribution of unrelated individuals did not deviate significantly from the Hardy-Weinberg expectation. Linkage of F13A with HLA was confirmed (z = 5.18, theta = 0.17 in males and z = 0.14, theta = 0.37 in females). The sequence of the three systems F13A, HLA and GLO was found to be F13A-HLA-GLO as judged from two families each with a recombinant within the HLA system in males.

Factor XIII↗

PubMed1986

An HLA-D region restriction fragment length polymorphism associated with celiac disease.

This study is the first to describe a molecular marker that distinguishes the celiac disease HLA-D region haplotype from a serologically identical haplotype in unaffected controls. Using a DQ beta chain cDNA probe and the restriction endonuclease Rsa I, we have detected a polymorphic 4.0 kb fragment which, in DQw2 individuals, is associated with a 40-fold increased relative risk of developing celiac disease. This finding should permit the identification of the celiac disease susceptibility gene(s) in the HLA-D region and facilitate a more precise dissection of the molecular and immunogenetic mechanisms involved in the pathogenesis of that disease.

Celiac Disease↗

PubMed1994

HLA and T-cell receptor polymorphisms in Belgian multiple sclerosis patients: no evidence for disease association with the T-cell receptor.

There are compelling data to indicate that the susceptibility to multiple sclerosis (MS) is inherited, at least in part. Particular HLA genotypes may be associated with MS and recently also polymorphisms in the T-cell receptor (TCR) genes have been reported to correlate with the disease; however, these data have been difficult to confirm. We investigated the TCRA and TCRB chain genes of HLA-typed Belgian CP MS patients employing four DNA restriction fragment length polymorphisms (RFLPs) detected with TCR constant (TCRAC1, TCRBC2) and variable (TCRBV8, TCRBV11) gene segments. Similar frequencies in patients and controls were observed for all RFLPs studied. Although the HLA DR2 genotype was significantly associated with MS, no interactive effects were seen with MS, DR2, TCRAC1, TCRBC2 and TCRBV alleles. We conclude that, while a clear association with HLA DR2 is observed, little convincing evidence exists for an association of CP MS with RFLPs of the TCRA or TCRB chain genes.

Alleles↗

PubMed1993

Polymorphism in the regulatory region of HLA-DRB genes correlating with haplotype evolution.

Class II genes of the human major histocompatibility complex (MHC) are polymorphic. Allelic variation of the coding region of these genes is involved in the antigen presentation and is associated with susceptibility to certain autoimmune diseases. The DR region is unique among human class II regions in that multiple DRB genes are expressed. Differential expression of the different DRB loci has been demonstrated, and we sequenced the proximal promoter region of the HLA-DRB genes, known to be involved in the regulation of these genes. We found locus-specific and allele-specific nucleotide variations in their regulatory regions and we determined the relationship between the regulatory regions of HLA-DRB genes. This polymorphism found in the regulatory conserved boxes could be involved in the observed differential expression of DRB loci. In addition, we found a polymorphism between the regulatory regions of DRB1 alleles which might be involved in an allele-specific regulation and therefore could be considered as an additional factor in susceptibility to autoimmune diseases.

Base Sequence↗

PubMed1992

HLA-DPB1 typing with polymerase chain reaction and restriction fragment length polymorphism technique in Danes.

We have used the polymerase chain reaction (PCR) in combination with the restriction fragment length polymorphism (RFLP) technique for HLA-DBP1 typing. After PCR amplification of the polymorphic second exon of the HLA-DPB1 locus, the PCR product was digested with seven allele-specific restriction endonucleases: RsaI, FokI, ApaI, SacI, BstUI, EcoNI, and DdeI, and the DNA fragments were separated by electrophoresis in agarose gels. Altogether, 71 individuals were investigated and 16 different HLA-DPB1 types were observed in 26 different heterozygotic combinations, as well as five possible homozygotes. Four heterozygotes could not be unequivocally typed with the PCR-RFLP method. The HLA-DPB1 typing results obtained with the PCR-RFLP method were compared with the typing results obtained with PCR allele-specific oligonucleotides (PCR-ASO) in 50 individuals. The results obtained with the two methods were concordant in 84% of the cases. One of the HLA-DPB1 types was discrepant in six heterozygotes, both HLA-DPB1 types were discrepant in one heterozygote, and in one individual two HLA-DPB1 types were identified with the PCR-RFLP technique while only one HLA-DPB1 type could be demonstrated with the PCR-ASO technique. The frequencies of the HLA-DPB1 genotypes deduced from the results of PCR-RFLP typing were estimated in 71 healthy Danes.

Adult↗

PubMed1989

Monoclonal antibody definition of the DRB3 allele, HLA-Dw25.

Monoclonal antibodies are powerful tools for analyzing HLA antigen polymorphism. We have investigated the serological and biochemical nature of the DRw52-related antigen defined by the monoclonal antibody NDS10. A detailed analysis of the population distribution of NDS10 reactivity revealed that the epitope was present on a subpopulation of DRw52 positive cells. A distinct pattern of reactivity was found within DR3 individuals: all of the B18,DR3 cells were NDS10 positive, whereas the A1,B8,DR3 cells were negative. All of the DR5(w11) cells and two of three DRw12 cells reacted with NDS10. NDS10 reactivity with DRw6 was not restricted to either of the serologically defined subtypes; three of 17 DRw13 and nine of 10 DRw14 cells were NDS10 positive. NDS10 was unreactive with all of the DRw8 cells tested. Two-dimensional gel analyses revealed that the NDS10 molecule precipitated from DR3, DR5(w11) and DRw6(w14) cell lines had an identical beta chain profile. These data indicate that NDS10 recognises the Dw25 allele of the DRw52 complex.

Antibodies, Monoclonal↗

PubMed2001

MICA genetic polymorphism and linkage disequilibrium with HLA-B in 29 African-American families.

The human major histocompatibility complex (MHC) class I chain-related gene A ( MICA) is located 46 kb upstream of HLA-B and encodes a stress-inducible protein which displays a restricted pattern of tissue expression. MICA molecules interact with NKG2D, augmenting the activation of natural killer cells, CD8(+) alpha beta T cells, and gamma delta T cells. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. We investigated MICA allelic variations and linkage disequilibrium with HLA-A, B, and DRB1 loci on 110 parental haplotypes from 29 African-American families. PCR/sequence-specific oligonucleotide probing (SSOP) was used to define MICA polymorphisms in exons 2, 3, and 4. Ambiguous allelic combinations were resolved by sequencing exons 2, 3, and 4. Exon 5 polymorphisms were analyzed by size sequencing. For HLA-A, B and DRB1 typing, low-resolution PCR/SSOP and allelic PCR/sequence-specific priming techniques were used. Twelve MICA alleles were observed, the most frequent of which were MICA*008, MICA*004, and MICA*002, with gene frequencies of 28.2, 26.4, and 25.5%, respectively. Thirty-eight HLA-B- MICA haplotypic combinations were uncovered, 22 of which have not been reported in the HLA homozygous typing cell lines from the 10th International Histocompatibility Workshop. Significant positive linkage disequilibria were found in 8 HLA-B- MICA haplotypes. Furthermore, haplotypes bearing HLA-B*1503, *1801, *4901, *5201, *5301, and *5703 were found to segregate with at least two different MICA alleles. Our results provide new data about MICA genetic polymorphisms in African-Americans, which will form the basis for future studies of MICA alleles in allogeneic stem cell transplantation outcome.

Alleles↗

PubMed2001

Transmission of high-risk HLA-DQB1 alleles in Chilean type 1 diabetic patients and their parents: stratification by the presence of ICA or GAD65 autoantibodies.

AIM: The purpose of this study was to assess whether the transmission of DQB1*0201 and DQB1*0302 alleles from heterozygous parents to Chilean type 1 diabetic patients depends on the presence of antibodies such as glutamic acid decarboxilase (GAD65) or Islet Cell (ICA) autoantibodies in the affected case. MATERIAL AND METHODS: A study of incident type 1 diabetic cases and parents was carried out in Santiago, Chile during 1997-98. The use of the case-parental design eliminates the possibility that case-controls differences are due to selection of controls whose genetic backgrounds differ systematically from those of cases. HLA-DQB1 polymorphisms were determined in cases and parents from n = 83 families using polymerase chain reaction and oligonucleotide dot-blot analysis. Detection of GAD65 antibodies was performed using a simple radio-binding asssay. Conventional ICA were detected by indirect immunofluorescence. RESULTS: Transmission disequilibrium test indicate a strong association between DQB1*0201 and DQB1*0302 and type I diabetes. When comparing the two subsets of families defined by having an affected child tested negative or positive for GAD65 antibodies (39 and 44 case-parent trios respectively) the probability of transmission of DQB1*0201 significantly differed between such strata (p-value=0.025). The pattern of transmission of DQB1*201 allele was also significantly different in the two subsets of families defined by ICA-or ICA+ cases (23 and 60 trios respectively) (p-value = 0.028). No differences were found in the transmission of DQB1*0302 allele in the different strata defined by the autoimmunity status of the proband. CONCLUSION: Our results reveal that DQB1*0201 allele may display distinct associations with type I diabetes depending on the autoimmunity to ICA and GAD65 autoantibodies.

Adolescent↗

PubMed1986

Identification of two subtypes of HLA-DR2 by Southern blot analysis.

We studied the polymorphism of HLA-DR2 by Southern blot analysis. Genomic DNA from 12 DR2 positive unrelated individuals was digested separately with five restriction endonucleases, Bam HI, Eco RI, Eco RV, Hind III and Pvu II. Hybridizing restriction fragments were visualized using radiolabeled beta-chain cDNA probes homologous to the DR and DQ subregions of the HLA. The results in the present study demonstrate that the two subtypes of DR2, DR2.1 and DR2.2, as defined by serological and cellular (PLT) techniques can be identified by Southern blot analysis. These two subtypes were identifiable after cleaving genomic DNA with Bam HI and EcoRV. DR2.1 correlated with restriction endonuclease fragments at 2.8 kb (DR beta) and 6.6 kb (DQ beta) after Bam HI digest, while DR2.2 correlated with a 2.9 kb (DR beta) and a 2.6 kb (DQ beta) restriction fragment after Eco RV digest. In addition, inheritance of the restriction fragment lengths defining DR2.1 and DR2.2 were observed in two families. In contrast, no differences between DR2.1 and DR2.2 were observed with the restriction enzymes Eco RI, Hind III and Pvu II.

DNA Restriction Enzymes↗

PubMed2005

Single nucleotide polymorphisms detection based on DNA microarray technology: HLA as a model.

The significance of DNA variations among individuals, including single nucleotide polymorphisms (SNPs) and/or genome nucleotide mutations as well as to their detection by using new technology, will improve and facilitate the knowledge of each gene sequence. Microarray may provide information about thousands of gene simultaneously, leading to a more rapid and accurate genotyping. In this view, we developed a new methodology as an example for the detection of SNPs based on DNA microarray, using a panel of HLA alleles representative of loci A, B, DRB1. A panel of 180 oligonucleotide probes was selected to identify polymorphic positions located in exons 2 and 3 of HLA-A and B, and in exon 2 of HLA-DRB1 locus. Each oligonucleotide sequence was designed with a nucleotide mismatch located in the same position as the center of the hybridization sequence. Hybridization experiments were carried out with genomic probes constructed with an asymmetric PCR strategy. The amplified DNAs were obtained from bone marrow cells of donors previously typed for transplant. The results obtained were showing that the method was reliable thus providing a feasible technique both for HLA typing and for the investigation of other regions of genetic and clinical interest including polymorphisms correlated with different autoimmune diseases.

Alleles↗

PubMedDate not supplied

A phase 1a clinical trial of LYM-1 monoclonal antibody serotherapy in patients with refractory B cell malignancies.

Ten patients with refractory B cell lymphomas were treated with weekly intravenous infusions of escalating doses of murine monoclonal antibody (MoAb) LYM-1 over four weeks. LYM-1 is a recently developed IgG2a murine MoAb that recognizes a polymorphic HLA-Dr antigen on surfaces of normal and malignant B cells but does not bind to any other normal tissues. MoAb LYM-1 has several advantages for serotherapy, since the antigen it recognizes is not shed from the cell surface and does not modulate in response to MoAb therapy. Furthermore, in vitro studies have indicated significant anti-tumour activity against lymphoma cell lines. In the current trial, dose-dependent levels of free LYM-1 were detected in the serum of all patients, but penetration of extravascular tumour tissues was poor. No significant toxicity or human anti-mouse antibody responses were observed in any patient. Clinical responses were minor and appeared to correlate with the number of infiltrating T cells seen in the initial lymphoma specimens. LYM-1 appears to be well-tolerated and has demonstrated several potential advantages as a therapeutic agent in patients with lymphoma. The mechanism of anti-tumour effect and plans for further clinical studies are discussed.

Adult↗

PubMed1995

NK cell recognition of major histocompatibility complex class I molecules.

Interactions between membrane receptors on NK cells and major histocompatibility complex (MHC) class I molecules on target cells inhibit NK cell-mediated cytotoxicity. In the mouse, receptors encoded by genes of the Ly-49 family bind certain polymorphic H-2 molecules and prevent lysis of normal hematopoietic cell targets. While a human homolog of Ly-49 has not been identified as yet, two structurally distinct NK cell-associated membrane glycoproteins, NKB1 and p58, have been implicated in the recognition of polymorphic HLA-B and HLA-C molecules, respectively. Recent studies indicate that human NK cell clones express multiple receptors for HLA class I molecules and suggest that these receptors may operate independently when expressed in a single NK cell clone.

Animals↗

PubMed1994

Analysis of the population of human T cell receptor gamma and delta chain variable region subfamilies by reverse dot blot hybridization.

We have developed a simple method to analyze the population of T cell receptor (TCR) gamma and delta chain variable (V) region subfamilies by the application of reverse dot blot hybridization, which was originally developed for the analysis of human HLA-DR polymorphism. The four oligonucleotides corresponding to each TCR-gamma V region subfamily and the six oligonucleotides to each TCR-delta V region gene were synthesized, and tailed with dTTP. The cDNA was amplified by ligation-mediated PCR in the presence of biotinylated deoxynucleotides. Hybridization between immobilized specific oligoprobes and biotinylated target DNA was nonradioactively detected by a reaction using alkaline phosphatase. The population of the V region subfamilies of TCR-gamma and -delta in PBL analyzed by reverse dot blot hybridization described here showed good correlations with the result of colony hybridization.

Base Sequence↗