Opinion: HLA-DRB alleles polymorphism in four ethnic populations in Northwestern China.
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China↗
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Results for “HLA polymorphism”
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Lack of association between transporter associated with antigen processing (TAP) and HLA-DM gene polymorphisms and antibody levels following measles vaccination.
The transporter associated with antigen processing (TAP) and human leukocyte antigen-DM (HLA-DM) genes are involved in the antigen-processing pathway of both HLA class I and class II-restricted antigen presentation. We hypothesized that polymorphisms within the TAP and DM genes may influence antibody levels following measles vaccination. We examined TAP and DM polymorphisms in 242 school children from Olmsted County, Minnesota, USA who received one dose of measles-mumps-rubella-II (MMR-II) vaccine at the age of 15 months. Based on the level of serum measles-specific immunoglobulin G (IgG) antibodies, subjects were classified as seronegatives (n = 72) or seropositives (n = 170). We determined TAP1 and TAP2 allele types by polymerase chain reaction (PCR) amplification of specific alleles (PASA) and determined DM allele type by PCR amplification followed by direct sequencing of the polymorphic sites. We analysed the data for any TAP or DM allelic association with antibody levels post measles vaccination using the chi-square test and univariate linear regression analysis. We found no trend in the overall distribution of TAP and DM genotype frequencies between seronegative and seropositive subjects, suggesting that TAP and DM polymorphism and antibody levels following measles vaccination are not directly associated. In addition, we did not find an association between TAP (TAP1, P = 0.71; TAP2, P = 0.87) or DM (DMA, P = 0.42; DMB, P = 0.71) homozygosity and seronegativity to measles vaccine in this study group. Our study suggests that TAP and DM gene polymorphisms do not influence antibody levels post measles vaccination.
ATP-Binding Cassette Transporters↗
HLA class II polymorphism in the Ticuna of Brazil: evolutionary implications of the DRB1*0807 allele.
The alleles at the HLA class II loci HLA-DRB1, DQA1, DQB1 and DPB1 were determined for 49 individuals of the Ticuna, a Native South American population living in Brazil, using PCR/SSO probe hybridization and DNA sequencing. A newly described DRB1*08 variant, DRB1*0807, which has previously been reported only in native Colombians and contemporary Brazilians of African and Caucasian descent, was identified in the Ticuna at a high frequency (f=0.225). Because *0807 has been observed only in South American populations, we propose that it was generated from a parental *0802 allele recently, after the isolation of various Native South American populations, and infer that the DRB1*0807 allele was generated by a C to T change at codon 57 (Asp-->Val, GAT-->GTT) from the ancestral *0802. This inference is supported by the sequence of a complex VNTR in the second intron of the DRB1 gene. The DPB1 alleles *0401, *0402 and *1401 constituted 76% of the observed Ticuna DPB1 alleles (f=0.166, 0.427 and 0.166 respectively). In addition, the DPB1 allele *3501, which has been observed in a few other Native South American groups, was observed at a frequency of 0.053 and may have been generated from the putative ancestral allele *1401 allele in South America. The DRB1 and DPB1 allele frequencies for the Ticuna deviate from expected Hardy-Weinberg equilibrium proportions, while DQA1 and DQB1 allele frequencies do not. When this deviation, which involves an observed excess of DRB1*0807 heterozygotes, is considered with the high frequency of the DRB1*0807 and DPB1*1401 alleles, we infer that native South American populations may have been under selection pressure for increased allele diversity.
Africa↗
HLA-DRB and -DQB1 polymorphism in the Macedonian population.
HLA-DRB1, DRB3/4/5 and DQB1 polymorphism has been studied in a population of 80 unrelated healthy Macedonians using molecular methods. Twenty-five different DRB1 alleles were identified of which DRB1*1104, *1501, *1601, and *1101 were found most frequently. Among the 15 identified DQB1 alleles, two were predominant: DQB1*0301 and *0502. The most frequent three-locus haplotypes were DRB1*1104-DRB3*02-DQB1*0301 (18%/), DRB1*1101-DRB3*02-DQB1*0301 (9%) and DRB1*1601-DRB5*02-DQB1*0502 (10%). Polymorphism for DRB1*04, *13 and *15 haplotypes was extensive. Eleven different DR2-related haplotypes were found, some of which were unusual for European populations: DRB1*1501-DRB5*0102-DQB1*0502, DRB1*1501-DRB5*02-DQB1*0502, DRB1*1501-DRB5*0102-DQB1*0601.
Alleles↗
Polymorphism of the HLA class II loci in Siberian populations.
The populations that colonized Siberia diverged from one another in the Paleolithic and evolved in isolation until today. These populations are therefore a rich source of information about the conditions under which the initial divergence of modern humans occurred. In the present study we used the HLA system, first, to investigate the evolution of the human major histocompatibility complex (MHC) itself, and second, to reveal the relationships among Siberian populations. We determined allelic frequencies at five HLA class II loci (DRB1, DQA1, DQB1, DPA1, and DPB1) in seven Siberian populations (Ket, Evenk, Koryak, Chukchi, Nivkh, Udege, and Siberian Eskimo) by the combination of single-stranded conformational polymorphism and DNA sequencing analysis. We then used the gene frequency data to deduce the HLA class II haplotypes and their frequencies. Despite high polymorphism at four of the five loci, no new alleles could be detected. This finding is consistent with a conserved evolution of human class II MHC genes. We found a high number of HLA class II haplotypes in Siberian populations. More haplotypes have been found in Siberia than in any other population. Some of the haplotypes are shared with non-Siberian populations, but most of them are new, and some represent "forbidden" combinations of DQA1 and DQB1 alleles. We suggest that a set of "public" haplotypes was brought to Siberia with the colonizers but that most of the new haplotypes were generated in Siberia by recombination and are part of a haplotype pool that is turning over rapidly. The allelic frequencies at the DRB1 locus divide the Siberian populations into eastern and central Siberian branches; only the former shows a clear genealogical relationship to Amerinds.
Alleles↗
HLA-B27 subtype polymorphism and CTL epitope choice: studies with EBV peptides link immunogenicity with stability of the B27:peptide complex.
HLA-B27-restricted CTL responses to EBV are principally directed against two of the EBV nuclear Ags, EBNAs 3B and 3C. We have previously described a target epitope derived from EBNA 3C (residues 258-266, sequence RRIYDLIEL) that is immunodominant in the context of at least three different B27 subtypes, including B*2705 and B*2702. In this study, we show that this peptide binds well to B*2705 and B*2702 in a cell surface binding assay, and that the two B27:peptide complexes are relatively stable, with t1/2 of 20 and 37 h, respectively. We now identify another B27-restricted epitope derived from EBNA 3B (residues 243-253, sequence RRARSLSAERY), which again accords well with the B*2705/B*2702 consensus motifs, having an arginine residue at position 2 and a tyrosine residue at the carboxyl terminus. In this case, five of five B*2702-positive donors respond to the epitope, whereas there was no response in any B*2705-positive donor studied. This peptide binds at least as well to B*2705 as to its restriction element B*2702; however, the two class I:peptide complexes show marked differences in stability, with t1/2 of 9 and 42 h, respectively. Thus, the stability of B27:peptide complexes can vary markedly between different B27 subtypes in ways that may not be apparent from cell surface binding assays and cannot be predicted from currently known peptide consensus motifs, yet which may critically influence CTL epitope choice.
Antigen Presentation↗
Influence of TNF gene polymorphism and HLA-DRB1 haplotype in Japanese patients with chronic liver disease caused by HCV.
OBJECTIVE: To clarify the host genomic role in chronic liver disease associated with hepatitis C virus (HCV), we investigated the relationship between the severity of hepatitis and the polymorphisms of the tumor necrosis factor (TNF) gene or the human leukocyte antigen (HLA)-DRB1 haplotypes. METHODS: We analyzed 40 healthy subjects, 50 patients with chronic inactive hepatitis caused by HCV with mean serum ALT concentrations under 40 IU/ml (group A), and 50 patients with chronic active liver disease caused by HCV and mean ALT concentrations over 50 IU/ml (group B). RESULTS: There were no significant differences in the frequencies of TNF promoter gene variants at positions -238 and -308 between the groups. Regarding polymorphisms at the TNF-beta NcoI site, the frequency of B1B1 homozygotes in group A was significantly increased, compared with the healthy subjects and those in group B (controls 7.5%, group A 34%, group B 10%). Regarding the analysis of HLA-DRB1, DRB1*0901 was significantly more frequent in group A than in group B (group A 19%, group B 5%). TNF B1B1 homozygotes were associated with HLA-DRB1*0901 and *1302, and negatively associated with DRB1*0405. Combination analysis revealed that HCV was inactive in the majority of patients who were both DRB1*0901 and B1B1 homozygotes. CONCLUSION: Our data suggest that TNF gene polymorphisms and HLA-DRB1 haplotype may influence the activity of HCV in chronic liver disease.
Female↗
Polymorphism of HLA-B27 in Taiwanese Chinese.
Heterogeneity of HLA-B27 is represented by a family of 24 closely related alleles/subtypes. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. Accurate investigation of frequencies of alleles is often hindered by the size and demographic region of sample tested. With an ever-increasing number of B27 alleles being discovered, it is becoming imperative to establish disease association of each individual alleles and its biological importance. In a large number of normal healthy Taiwanese Chinese individuals (75,777) tested nationally, over a period of five years, in a single immunogenetics centre, we found additional B27 subtypes not revealed in a previous Taiwanese Chinese population study. The subtypes found in Taiwanese Chinese and the frequencies of each of the subtypes are reported.
Adolescent↗
Nucleotide sequence of HLA-B*5505, which expresses a unique HLA class I polymorphism.
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Alleles↗
HLA-G expression in placenta in relation to HLA-G genotype and polymorphisms.
PROBLEM: The expression of the non-classical human leukocyte antigen (HLA) class Ib gene, HLA-G, seems to be important at the feto-maternal interface. The HLA-G molecule is almost monomorphic and expressed in both membrane-bound and soluble isoforms. It has been shown to inhibit natural killer cell -mediated lysis and influence cytokine expression. HLA-G gene polymorphism has been linked to differences in gene expression profile of alternatively spliced HLA-G transcripts and levels of specific HLA-G messenger RNA (mRNA) isoforms. Furthermore, aberrant HLA-G expression has been reported in preeclamptic placentas. On this background it is of general interest to further elucidate any associations between HLA-G polymorphism and protein expression. METHODS: We have investigated HLA-G protein expression by immunohistochemistry in HLA-G genotyped placentas from term. HLA-G mRNA expression in preeclamptic placentas and in control placentas was also studied by microarray technology. RESULTS AND CONCLUSIONS: The studies of HLA-G protein expression in term placentas by immunohistochemical analysis showed no clear associations with HLA-G genotypes although this could be because of the very semi-quantitative nature of this technique. However, we found a tendency towards reduction of HLA-G mRNA expression in placentas from preeclamptic cases compared to matched controls with the use of microarray technology.
Biopsy↗
HLA-DR beta gene DNA polymorphisms revealed by Taq I correlate with HLA-DR specificities.
Human genomic DNA digested with restriction endonuclease Taq I was hybridized with cDNA probes for DR beta and DQ beta, for correlation of restriction fragment length polymorphisms with HLA-DR specificities. DR beta Taq I RFLPs were distinctive for DR serological types 1 to w9, with the exception of DR3 and w6, and were markedly consistent within DR specificity. Some common variants in RFLPs did emerge within serological type; DR3, e.g., was associated with two different fragment patterns, one of which occurred on the A1.B8.DR3 haplotype and was linked with a DR alpha Bgl II variant, and the other on the B18.DR3 haplotype. In the Pacific specimens examined, RFLPs were, with few exceptions, similar to those seen in Caucasoids sharing the same DR specificity. This study indicates that genomic hybridization is a useful adjunct to serological and cellular class II typing and should be particularly informative in identifying new HLA-DR alleles in populations serologically less well-defined than Caucasoids.
Black People↗
Correlation between HLA-DR sequence polymorphisms and rheumatoid factor production.
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Alleles↗
DNA restriction fragment length polymorphism of HLA-DR2: correlation with HLA-DR2-associated functions.
HLA-DR2 can be divided into at least 3 distinct HLA-D clusters which correlate with structural differences within the HLA-D region. Further, a functional counterpart of this subdivision has been previously identified. The presence of a particular DR beta 2 polypeptide chain correlated precisely with the susceptibility of measles virus-infected HLA-DR2 homozygous typing cell lines to lysis by measles virus-specific, HLA class II-restricted CTL clones. To determine if a genetic basis for these functional differences could be detected, the degree of polymorphism at the DNA level within the serologically defined HLA-DR2 haplotype has been examined. By using DNA probes for DR beta and DQ beta 4 of the 5 HLA-D clusters of HLA-DR2 could be distinguished and a RFLP pattern was identified which correlates with known immunological functions associated with these various D types. In addition, this technique of 'molecular genotyping' was used to investigate a limited panel of patients with multiple sclerosis (MS) who were HLA typed as either HLA-DR2,2 or HLA-DR2,blank. The RFLP profile of the HLA-DR2 Dw2 D type was found in all of these MS patients.
Cell Line↗
Polymorphism of the HLA DR1 haplotype in the Israeli population investigated at the serological, cellular, and genomic levels.
In the present report, we used serological, cellular, and restriction fragment length polymorphism (RFLP) to investigate the DR1 haplotype in the Israeli population. We describe an Israeli homozygous typing cell (HTC), HLA-Dw"LVA", which defines a new lymphocyte-activating determinant associated with Bw65, DR1 and distinct from Dw1. The parents of this donor, non-Ashkenazi Algerian Jews, are first cousins and share HLA-Cw8,Bw65,BfS,DR1,DQw1,DPw4. No specificity could be assigned to HLA-Dw"LVA" using the 91 Ninth Workshop HTCs. Two families and forty unrelated DR1 individuals were studied with Dw"LVA" and a panel of DR1/Dw1 HTCs. HLA-Dw"LVA" showed segregation as a single determinant within families. This new specificity was present in 24 out of 40 (60%) unrelated DR1 individuals, indicating that in the Israeli population Dw"LVA" is the main lymphocyte-defined determinant associated with the serologically defined DR1 specificity, in contrast to non-Jewish Caucasoids where DR1 is significantly associated with Dw1. The vast majority of Dw"LVA"-positive carriers were also Bw65 carriers, indicating that Bw65,DR1, Dw"LVA" may represent a typical allele combination in the Israeli population. The RFLP analysis established the correlation of certain RFLPs with Dw1 and Dw"LVA". In addition, we describe a cluster of FRLPs that may correspond to a new Dw subtype associated with DR1, for which no serological and cellular reagents have been described so far.
DNA Restriction Enzymes↗
[Genetic polymorphism of HLA-Cw locus in hematopoietic stem cell transplantation patient and donor population].
OBJECTIVE: To analyze the distribution of genes in HLA-Cw locus from Han population of China in a large scale, and to provide basic data for further study on the genetic characteristics of HLA-Cw locus of this population. METHODS: Totally 1285 unrelated Chinese Han individuals were typed by PCR-SSP, and statistics was utilized to investigate the distribution rules of detected genes. RESULTS: Twenty-three HLA-Cw alleles were identified in Chinese Han population, out of them HLA-Cw*01, *03, *07 and *08 were the commonest genes, which accounted for frequencies of 0.1529, 0.2385, 0.1747 and 0.1004, respectively. Five genes which could not be identified by serological method were deaed: HLA-Cw*12, *14, *15, *16 and *17. Hardy-Weinberg test showed that the observed genetic polymorphism distribution values were correspondent with the expected (chi-square=73.74, df=98, P>0.5). CONCLUSION: This study may serve a full-scale scientific genetic parameters of HLA-Cw genes for Chinese Han population studies.
Adolescent↗
Susceptibility to insulin-dependent diabetes defined by restriction enzyme polymorphism of HLA-D region genomic DNA.
DNA fragments complementary to cloned sequences encoding HLA-D region class II antigen alpha- and beta-chains were determined by genomic blotting with DNA from HLA-typed members of 22 complete families, 12 of which had a proband with insulin-dependent diabetes mellitus (IDDM). Analysis of genotypes showed that the DNA sequences were linked to HLA-DR and permitted confirmation of recombinations in two families. Digestion with the restriction enzymes BamHI, EcoRI, and PstI and hybridization with an HLA-D region beta-chain cDNA probe confirmed a BamHI 3.7 kilobase (kb) fragment present at low frequency among diabetic individuals and a BamHI 3.2 kb fragment that was also decreased among the diabetic subjects compared with siblings (P less than 0.05) as well as nonrelated control siblings (P less than 0.02) and their parents (P less than 0.01). BamHI 12.0 kb (P less than 0.05) and 5.8 kb (P less than 0.02, P less than 0.02), EcoRI 20 kb (P less than 0.05, P less than 0.02), and PstI 6.0 kb (P less than 0.05) fragments were more frequent in diabetic individuals compared with nonrelated control siblings or their parents, respectively. Analysis of individual haplotypes revealed that HLA-DR4-containing chromosomes were heterogeneous among controls but that the diabetic individuals showed a similar pattern of restriction fragment length polymorphism. Genomic blotting of blood lymphocyte DNA with a cDNA clone encoding the chain of HLA-D region class II antigens permits detection of fragments that are strongly associated with IDDM.
Adolescent↗
Polymorphisms of HLA-DR and -DQ genes in Japanese patients with bullous pemphigoid.
Bullous pemphigoid (BP), an autoimmune skin disease of the elderly, is mediated by autoantibodies that bind to hemidesmosomes of epidermal basal cells. This study investigated BP-associated HLA-DR and -DQ genes among Japanese patients. We analyzed HLA-DR and -DQ genes among 23 Japanese BP patients based on the polymerase chain reaction-restriction fragment length polymorphism. Eighteen of these 23 patients (78%) carried at least one allele of HLA-DRB1*04 or DRB1*1101, with significant increases in HLA-DRB1*04 (*0403, *0406)/DQA1*0301/DQB1*0302 and DRB1*1101/DQA1*0505/DQB1*0302 haplotypes as well as the individual alleles DRB1*1101 and DQB1*0302 (corrected p < 0.05 for each comparison), when compared to control subjects. These data differ from the accepted DQB1*0301 (DQ7) association with the same disease among Caucasians. These findings indicate that different HLA class II haplotypes genetically influence susceptibility to BP among different ethnic groups. Our findings, together with previous reports on Caucasian patients with the pemphigoid group of bullous diseases, suggest that HLA-DRB1 molecules might participate in the regulation of autoimmune responses to BP antigens.
Aged↗
Reactivity of anti-HLA class I polymorphic monoclonal antibodies with normal human skin.
In this work the reactivity of 16 monoclonal antibodies raised against different HLA class I specificities was tested with human skin of healthy donors of known HLA typing. By indirect immunofluorescence, six antibodies reacted strongly with keratinocytes carrying the corresponding alloantigens. The reactivity of 3 other antibodies which was weak or absent using indirect immunofluorescence, was enhanced by various amplification systems such as avidin-biotin-peroxidase method, biotin-streptavidin-fluorescein complex and especially preliminary trypsin treatment that revealed alloantigens masked in the epidermis. The immunostaining of 4 antibodies was negative regardless of the method used. Some of the antibodies we tested cross-reacted with cytoplasmic antigens of keratinocytes. This study has allowed to select a battery of monoclonal antibodies which can specifically detect alloantigens on keratinocytes and will be useful for the recognition the cell origin in allografting experiments.
Antibodies, Monoclonal↗