PubMed Health⌕ Search

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 145 records · Page 8Linked to original sources
PubMed1992

Haplospecific polymorphism between HLA B and tumor necrosis factor.

Polymorphisms were sought between HLA B and tumor necrosis factor (TNF) using three genomic probes. Extensive polymorphism was detected within a panel of 50 cell lines including 37 homozygotes representing 21 different ancestral haplotypes (AH). Following Taq I digestion of genomic DNA, we observed three allelic patterns with probe X (R17A) and four with probe V (R9A). Seven different allelic patterns were found with probe Y (M20A) after Taq I + Rsa I digestion. Family studies showed that the Y, X, and V alleles were inherited and segregated with HLA haplotypes. A striking feature of the allelic patterns detected by these probes was that cells with the same AH had identical Y, X, and V alleles (i.e., the alleles were haplotypic). Of 15 different Y-X-V haplotypes observed, 11 were found to be specific for a particular AH (i.e., were haplospecific). Four were shared by more than one AH, but in these instances there were extensive similarities in other regions within the major histocompatibility complex (MHC), for example, the Japanese 46.2 (HLA Bw46-DRw8) and the Chinese 46.1 (Bw46-DR9) share all alleles between HLA C and C4 and differ only in class II, suggesting their relatively recent divergence by recombination between C4 and DR. Surprisingly, two insulin-dependent diabetes mellitus (IDDM)-resistant but race-specific AHs 52.1 (Bw52-DRB1*1502, Japanese) and 7.1 (B7-DRB1*1501, Caucasoid) carry the same Y-X-V haplotype, suggesting the possibility of localizing gene(s) relevant to IDDM. The present study confirms that MHC AHs have been conserved en bloc, including the region between HLA B and TNF.

Alleles↗
PubMed1981

Monoclonal rat anti-MHC alloantibodies detect HLA-linked polymorphisms in humans.

Two monoclonal rat anti-MHC alloantibodies detect a polymorphic determinant expressed on the peripheral lymphocytes of normal human donors. The pattern of cytotoxicity observed with these antibodies correlated with the HLA type of the individual; no HLA-A-locus specificities showed significant associations, and all of the HLA-B-locus specificities showing significant association were members of the Bw6 supertype. Family studies established that the determinant detected by the monoclonal antibodies is linked to HLA. These studies therefore provide an alternative basis for the production of monoclonal antibodies to polymorphic HLA determinants based on the conservation of polymorphic MHC determinants between man and rats.

Animals↗
PubMed1997

Sociobiology and HLA genetic polymorphism in hill tribes, the Irula of the Nilgiri hills and the Malayali of the Shevroy hills, south India.

Two endogamous tribes of Tamil Nadu, South India, the Irula of the Nilgiri hills and the Malayali of the Shevroy hills, were studied for their sociobiology and HLA polymorphism. For sociobiological studies 166 marriages in the Irula and 368 marriages in the Malayali were recorded. The number and spatial distribution of patrilineal clans and their marriageable range (number of clans from which the brides came) were studied. Eight clans in the Irula and 16 clans in the Malayali were identified. Of these the Kuppar of the Irula and the Malayan of Malayali were the largest clans, and both of them had the greatest marriageable range. The numerical strength and the resultant spatial distribution correlated well with the marriageable range. HLA-A, B, and DR polymorphism was studied on 191 Irula and 42 Malayali following standard procedures. HLA typing revealed high frequencies (> 10%) of alleles HLA-A2, A9, A11, B17, B35, B40, DR2, and DR7 in both tribes, but the Irula had elevated HLA-A10, B8, and DR8 frequencies and the Malayali had elevated HLA-A31, B7, DR4, and DR5 frequencies. Two-locus haplotypes A10-B8 and A2-B5 were identified in both tribes, but A11-B40 and A2-B53 were present only in the Irula and A33-B44 and B15-DR6 were present only in the Malayali. The sociobiology of the Irula was correlated to the HLA genetic profile. The Irula sample was stratified based on clan and HLA data; The Kuppar clan was closer to the Kalkatti, the second largest clan, than to the Pungar and the Sambar clans. Thus the numerical strength and spatial distribution of various exogamous clans, presumably a result of migration during different periods of history, is reflected in the marriageable range and thus in the genetic distance. In studying HLA or any other genetic polymorphism of an endogamous tribe or caste, one needs to consider the social structure, spatial distribution, and marriageable range.

Emigration and Immigration↗
PubMed2003

[The study of HLA-Cw polymorphism in Uygur population].

The HLA-Cw loci polymorphism in Uygur population was investigated using the PCR- sequence specific oligonucleotide probe (SSOP) method,and the genetic database on the distribution of gene frequency of the HLA-Cw loci was established. From 146 individuals of Uygur population,18 HLA-Cw alleles were detected. The gene frequency was from 0.0069 to 0.2460. The four most common alleles were HLA-Cw*04(24.60%),07(11.51%),08(10 10%),14(12.02%),and they covered 58.23% of total alleles detected from Uygur population.We have made a survey of HLA-Cw alleles frequencies in a Uygur population,with blank frequency being lowered to 0.0064. The distribution of genotype frequencies met the law of Hardy-Weinberg equilibrium by hi-square test. The frequency data can be used in forensic and paternity tests to estimate the frequency of a DNA profile in the Uygur population,transplant matching and anthropology.

English Abstract↗
PubMed2006

Virus-epitope vaccine design: informatic matching the HLA-I polymorphism to the virus genome.

Attempts to develop peptide vaccines, based on a limited number of peptides face two problems: HLA polymorphism and the high mutation rate of viral epitopes. We have developed a new genomic method that ensures maximal coverage and thus maximal applicability of the peptide vaccine. The same method also promises a large number of epitopes per HLA to prevent escape via mutations. Our design can be applied swiftly in order to face rapidly emerging viral diseases. We use a genomic scan of all candidate peptides and join them optimally. For a given virus, we use algorithms computing: peptide cleavage probability, transfer through TAP and MHC binding for a large number of HLA alleles. The resulting peptide libraries are pruned for peptides that are not conserved or are too similar to self peptides. We then use a genetic algorithm to produce an optimal protein composed of peptides from this list properly ordered for cleavage. The selected peptides represent an optimal combination to cover all HLA alleles and all viral proteins. We have applied this method to HCV and found that some HCV proteins (mainly envelope proteins) represent much less peptide than expected. A more detailed analysis of the peptide variability shows a balance between the attempts of the immune system to detect less mutating peptides, and the attempts of viruses to mutate peptides and avoid detection by the immune system. In order to show the applicability of our method, we have further used it on HIV-I, Influenza H3N2 and the Avian Flu Viruses.

Amino Acid Sequence↗
PubMed1996

HLA-DRB1 polymorphism determines susceptibility to autoimmune thyroiditis in transgenic mice: definitive association with HLA-DRB1*0301 (DR3) gene.

Familial clustering of autoimmune thyroid diseases has led to studies of their association with human major histocompatibility complex (MHC) class II genes. One such gene implicated in Hashimoto's thyroiditis (HT) is HLA-DR3, but the association is weak and is contradicted by other reports. On the other hand, murine experimental autoimmune thyroiditis (EAT), a model for HT, presents a clear linkage with MHC class II. Moreover, it is inducible with thyroglobulin (Tg), the common autoantigen in either species. Immunization of HLA-DRB1* 0301 (DR3) transgenic mice with mouse or human Tg resulted in severe thyroiditis. In contrast, transgenic mice expressing the HLA-DRB1*1502 (DR2) gene were resistant to EAT. Our studies show that HLA-DRB1 polymorphism determines susceptibility to autoimmune thyroiditis and implicate Tg as an important autoantigen.

Animals↗
PubMed2006

Importance of HLA-DQ and HLA-DP polymorphisms in cytokine responses to naturally processed HLA-DR-derived measles virus peptides.

We studied the association between class II human leukocyte antigen (HLA)-DRB1*0301 presented measles virus (MV) peptide-specific cytokine responses and DQB1 and DPB1 alleles among 313 individuals who received two doses of measles-mumps-rubella-II vaccine. The overall median IFN-gamma secretion levels (first and third quartiles) for the 19-amino acid MV phosphoprotein (MV-P)- and 14-amino acid MV nucleoprotein (MV-N)-derived peptides were 27.7 pg/ml (1.8, 109.4) and 1.9 pg/ml (-6.2, 13.0), respectively; median IL-4 secretion levels were -0.6 pg/ml (-7.1, 6.2) and 2.4 pg/ml (-3.2, 9.3), respectively. Primary statistical analyses were adjusted for previously identified DRB1 associations. A marginally significant increase in the frequency of the DQB1*0604 (p=0.02) allele was found among subjects who demonstrated detectable IL-4 levels to the MV-P peptide. Further, DPB1*0201 (p=0.02) and DPB1*1301 (p=0.09) alleles provided suggestive evidence of an association with MV-P-induced IL-4 secretion. Examination of IFN-gamma responses to MV-P and MV-N indicated that none of the individual alleles of the DQB1 and DPB1 loci were associated with peptide-induced T cell response. An increase in the frequency of DPB1*0501 (p=0.01) was found among subjects who failed to produce MV-N peptide-specific IL-4 responses. These data further confirm that HLA-DRB1 alleles are the major restriction molecules for MV-P and MV-N measles virus antigen presentation to T cells. We speculate that MV-P and MV-N peptides derived from DRB1*0301 could potentially be recognized in association with different HLA molecules, including DQB1 and DPB1; however, statistical adjustments for the effect of HLA-DR locus could potentially alter these genetic relationships. This concept provides important information supporting the use of promiscuous peptides in a peptide-based vaccine approach.

Adolescent↗
PubMed1998

[Simple and rapid detection of HLA-DRB polymorphism from forensic samples].

Simple and rapid detection of HLA-DRB polymorphism has been performed using AMPLICOR HLA-DRB Typing Kit. We tried to apply this kit to various forensic samples. When DNA was extracted from the forensic samples using conventional phenol-chloroform method, addition of 7.5 mM MgCl2 was required to PCR amplification. HLA-DRB types were detected from DNA more than 0.1 ng by PCR amplification. Typing of unrelated 50 Japanese showed 38 different patterns, of which 30 patterns occurred once in the group. A total of 16 serotypes were deduced from the HLA-DRB DNA types. Out of them, high frequency serotypes were DR4 (24%), DR9 (18%) and DR15/16 (14%). This kit was very useful in forensic cases such as rape and in paternity cases. When we tried to detect HLA-DRB types from a single hair shaft of 3 cm in length, we were successful in detection from only one of five persons.

Alleles↗
PubMed1999

Human leukocyte antigens and cancer: is it in our genes?

Human leukocyte antigens (HLAs) are widely expressed cell surface molecules which present antigenic peptides to T-lymphocytes, thus modulating the immune response. The efficiency of peptide presentation by HLAs is dependent on the extreme polymorphism in the HLA-encoding loci within the major histocompatibility complex (MHC). HLA polymorphism is known to alter disease susceptibility and progression in a range of predominantly inflammatory conditions, many of which are T-lymphocyte-mediated. More recently, the importance of alterations in HLA expression and polymorphisms within HLA-encoding loci has emerged in the development of malignancy. This review concentrates on the role of HLA polymorphism in malignant disease, with discussion of the major cancers in which HLA associations have become clear, as well as the potential mechanisms by which HLA polymorphisms may act as important factors, or cofactors, in the pathogenesis of malignant disease. In addition, the role of certain non-HLA genes within the MHC in the pathogenesis of malignancy is also considered briefly.

Cell Transformation, Neoplastic↗
PubMed2005

[HLA-B27 polymorphism and spondyloarthropathies].

The association of HLA-B27 with ankylosing spondylitis (AS), and other spondyloarthropathies (SpA), remains as one of the strongest between HLA molecules and human disease. Since it was reported, in 1973, it has been extensively studied in order to understand the underlying pathogenic mechanism. The objective of this article is to review the current knowledge on the structure and polymorphism of HLA-B27 molecule, as well as describe the main pathogenic hypotheses trying to explain its association with AS.

HLA-B27 Antigen↗
PubMed2004

Analysis of human leukocyte antigen (HLA)-G polymorphism in normal women and in women with recurrent spontaneous abortions.

Human leukocyte antigen (HLA)-G is a non-classical class I antigen. It has limited expression, but is high at the foetomaternal interface. This unique expression pattern of HLA-G suggests that it might be important for survival of the foetus during pregnancy. In the present study, 120 women with recurrent spontaneous abortions (RSA) and 120 fertile control women were genotyped for the HLA-G locus. This is the first report describing HLA-G polymorphism in normal fertile and RSA women from India. The allele HLA-G*010103 was higher in women with recurrent foetal losses. Interestingly, the HLA-G*010105 and G*010108 alleles were totally absent in normal fertile women but present in RSA women with frequencies of 1.7% and 0.4%, respectively. Allele G*010107 was absent in both the groups. The frequency of the null allele G*0105N was high (13.8%) in our population as compared to other world populations. Our data support the hypothesis that HLA-G polymorphism may contribute to recurrent foetal loss.

Abortion, Habitual↗
PubMed1994

HLA-G polymorphisms in African Americans.

HLA-G is a class I MHC gene most notable for its restricted tissue distribution. The unique expression of this gene in extravillous cytotrophoblast at the maternal-fetal interface suggests that HLA-G plays a critical role in human pregnancy. Previous studies have reported that HLA-G has a limited repertoire of rare alleles, unlike the classical class I alleles, which are among the most polymorphic human genes. To determine the full extent of sequence variation in this gene, we examined the nucleotide variation in the first six exons of this gene in 45 healthy African American persons. By using sensitive techniques that detect > 95% of nucleotide substitutions, we detected two sequence variations in the alpha-1 domain (exon 2) and 24 sequence variations in the alpha-2 domain (exon 3) that result in amino acid substitutions. These data indicate that HLA-G is potentially capable of presenting a wide variety of peptides and of eliciting an allogeneic response, similar to the classical class I HLA genes.

Adult↗
PubMed1992

Distribution of polymorphic HLA-DR and -DQ alleles as determined by restriction fragment length polymorphism analysis in an Austrian population.

The restriction fragment length polymorphism (RFLP) of HLA-DR beta, -DQ alpha and -DQ beta genes was analyzed in 637 unrelated individuals from the Austrian population. The restriction enzyme was Taq I, and three exon-specific probes were applied. The gene frequencies, the Hardy-Weinberg equilibrium in DR beta and DQ loci, linkage disequilibria between the loci and haplotype frequencies are calculated. Rare associations between DR and DQ loci are described. Two RFLP patterns are demonstrated which were unique in the overall 1,000 individuals tested so far.

Alleles↗
PubMed2000

HLA-G and HLA-E polymorphisms in an indigenous African population. The ZVITAMBO Study Group.

Studies of HLA-G and HLA-E polymorphisms in different populations from many industrialized countries have uniformly reported little sequence variation within these genes. To date, the polymorphism of these genes has not been characterized in populations from developing countries where more sequence variation would be anticipated due to greater exposure to microbial pathogens. In order to address this issue, we have recently investigated the polymorphism of these MHC genes in an indigenous African population (Shona ethnic group). HLA-G and HLA-E alleles were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS) analysis in 108 unrelated women recruited from maternity clinics and hospitals in Harare (Zimbabwe). The genotyping analysis identified six different HLA-G alleles and three HLA-E alleles in this population. Of interest, the null-allele HLA-G*0105N was found with 11.1% of frequency, which is higher than in other populations tested so far. We observed the presence of 15 distinct HLA-G genotypes and 6 HLA-E genotypes. These data indicate that this African population contains low levels of allelic polymorphism similar to ethnic groups from industrialized countries. This is the first report describing HLA-G and HLA-E polymorphisms in an indigenous African population.

Africa↗
PubMed1997

HLA-DM polymorphisms do not associate with multiple sclerosis: an association study with analysis of myelin basic protein T cell specificity.

The MHC region on 6p harbors at least one susceptibility gene for multiple sclerosis (MS). Within this region, HLA-DM loci are of interest being involved in class II antigen processing. We investigated the association of HLA-DM polymorphisms with MS. Sixty-three patients with MS and 46 healthy controls from continental Italy were typed for HLA-DM polymorphisms and HLA-DRB1 alleles. Besides, among the donors characterized for the DM polymorphisms, we considered 6 MS patients previously studied for the fine specificity of their MBP-specific T lymphocyte lines (TLL). The frequencies of allelic variants at the DMA and DMB loci were similar between MS patients and controls, even when HLA-DRB1*1501 positive and negative donors were analyzed separately. Patients with predominant responses to different MBP epitopes did not differ for their HLA-DM haplotype while patients with predominant responses to the same MBP epitope could present different HLA-DM haplotypes. HLA-DM polymorphisms do not associate with MS and may not affect specific patterns of T cell responses to MBP.

Adult↗
PubMed1997

Molecular analysis of HLA-DR polymorphism in polymyalgia rheumatica. Swiss Group for Research on HLA in Polymyalgia Rheumatica.

OBJECTIVE: To analyze by molecular typing possible associations of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) compared to controls and patients with rheumatoid arthritis (RA) in Switzerland. METHODS: In a multicenter survey, we recruited 100 patients with PMR with and without signs of giant cell arteritis (GCA), 198 with RA, and 200 controls (volunteer bone marrow donors). HLA-DR generic typing was performed by microtiter plate oligotyping and DR4 subtypes analyzed by dot blot hybridization with sequence specific oligonucleotides or by polymerase chain reaction sequence specific primers. RESULTS: DR4 and DR1 tended to be increased in PMR, compared to controls (36 vs 30%, p = 0.30; and 19 vs 12%, p = 0.16, respectively). Frequencies of all RA associated DR4 and DR1 subtypes tended to be increased in PMR as well. Frequency of the HLA-DR beta 1 70-74 shared motif (QK/RRAA) was significantly higher in PMR than in controls [50 vs 36%, odds ratio (OR) = 1.8, p = 0.018], although lower than in RA (77 vs 36%, OR = 6.0, p < 0.0001), and slightly out of the range of significance if a Bonferroni correction was applied (p = 0.1). At double dose, this epitope was also increased in PMR, but not significantly (5 vs 2%, OR = 2.6, p = 0.17), while it was markedly augmented in RA (22 vs 2%, OR = 14, p = < 0.0001). In patients with the shared epitope, the frequency of clinical signs of GCA tended to be increased (19 vs 10%, p = 0.25). Frequency of the HLA-DR beta 1 DRYF 28-31 motif was identical in PMR (95%) and controls (93%). CONCLUSION: PMR may be associated with the HLA-DR beta 1 70-74 shared epitope. This association, however, would be much weaker for PMR than for RA, particularly with the shared epitope at double dose. PMR is clearly not associated with the HLA-DR beta 1 DRYF 28-31 motif.

Aged↗
PubMed2006

HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortion.

Reproduction is an important biological phenomenon posing an immunological paradox because the semiallogeneic fetus survives by evading maternal immune recognition. The detailed mechanisms behind this maternal-fetal immunotolerance remain elusive. Human leucocyte antigen (HLA)-G, a non-classical HLA class I antigen, initially identified as a molecule selectively expressed on extravillous cytotrophoblasts and first studied in the context of pregnancy, has long been supposed to play a critical role in fetal-maternal immunotolerance. To investigate the role of HLA-G polymorphism in this process and whether the HLA-G genotype is associated with an increased risk for a subsequent miscarriage, 69 women with three or more recurrent spontaneous abortions (RSA) and 146 fertile control women were genotyped for the HLA-G locus in this study. To our knowledge, this is the first report on HLA-G polymorphism in RSA and in normal fertile women from a Chinese Han population. Nine HLA-G alleles were detected in the fertile control group; however, the allele HLA-G*0103 was absent in the RSA group. No statistical significance was observed in the distribution of HLA-G alleles between the two groups. The frequency of the null allele HLA-G*0105 N in the RSA group and in normal fertile women is 0.7% and 1.4%, respectively. Our data suggested that there was no association of HLA-G polymorphism with RSA.

Abortion, Habitual↗