Association between HLA-DQB1 gene and patients with acute lymphoblastic leukemia (ALL) (original) (raw)
Related papers
Molecular analysis of HLA-DQB1 alleles in childhood common acute lymphoblastic leukaemia
British journal of cancer, 1996
Epidemiological studies suggest that childhood common acute lymphoblastic leukaemia (c-ALL) may be the rare outcome of early post-natal infection with a common infectious agent. One of the factors that may determine whether a child succumbs to c-ALL is how it responds to the candidate infection. Since immune responses to infection are under the partial control of (human leucocyte antigen) HLA genes, an association between an HLA allele and c-ALL could provide support for an infectious aetiology. To define the limit of c-ALL susceptibility within the HLA region, we have compared HLA-DQB1 allele frequencies in a cohort of 62 children with c-ALL with 76 newborn controls, using group-specific polymerase chain reaction (PCR) amplification, and single-strand conformation polymorphism (SSCP) analysis. We find that a significant excess of children with c-ALL type for DQB1*05 [relative risk (RR): 2.54, uncorrected P=0.038], and a marginal excess with DQB1*0501 (RR: 2.18; P=0.095). Only 3 of ...
Revista de Chimie
The aim was to determine the prevalence of celiac disease (CD) in a pediatric population with juvenile idiopathic arthritis (JIA) and autoimmune hepatitis (AIH) compared to controls and to evaluate the clinical forms and human leukocyte antigen (HLA) alelles. Between September 2009-November 2019, 74 pediatric patients with JIA (1), 62 AIH (2) and 60 controls were assessed for CD. All children with one or more positive CD antibodies were submitted to gastrointestinal endoscopy with intestinal biopsy. All patients underwent HLA molecular assessment for DQ2/DQ8 alleles. Celiac prevalence after screening was 6.7% in the first group, 6.4% in the second group and 0% among controls. The results didn�t reveal significant differences regarding the CD prevalence among patients with JIA and AIH (p = 0.94). The majority of cases associated the silent form of disease (77.7). DQ2/DQ8 haplotypes were found in all CD cases. Of 69 children with JIA and no CD, three (4.3%) had DQ2 haplotype. Of 58 pa...
173-P HLA-DQA1 locus sequencing assay
Human Immunology, 2011
Human leukocyte antigen (HLA)-DQB1*03:19 differs from HLA-DQB1*03:01 in only one position in exon 3. Until recently both alleles were commonly reported as HLA-DQB1*03:01g, thus prompting this study on relative frequency of these alleles and their possible haplotype associations. Methods: Relative frequencies of DQB1*03:19 and DQB1*03:01 were determined by Luminex Based sequence-Specific Oligonucleotide Probes (SSOP, One Lambda Inc) in 427 subjects carrying DQB1*03:01/03: 19 alleles including 341 Caucasians (C), 72 African Americans (AF) and 14 Hispanics (H). Results: Of 427 consecutive individuals carrying DQB1*03:01/03:19, 53 (12.4%) were DQB1*03:19 (9 C, 42 AF and 2H) and 374 (87.6%) were DQB1*03:01 (332 C, 30 AF and 12 H). In this cohort, the most commonly observed associations of DQB1*03:19 with various DQA1, DRB1, and DRB3 alleles are reflected in 5 four-locus haplotypes.
1987
HLA-DR and -DQ serotyped cell lines and peripheral blood leucocytes were analysed by Southern blot allogenotyping. Using a short DQB cDNA probe, a DQB allelic series was defined by restriction fragment length polymorphism (RFLP) with the restriction endonuclease Z'aqI. This DQB allelic series correlates with, and defines splits of, the HLA-DQ serological specificities DQwl (DQ/I la and DQB lb RFLPs), DQw2 (DQp2a and DQp2b RFLPs) and DQw3 (DQ/?3a and DQp3b RFLPs). By sequential use of a short DQG( cDNA probe a second, DQa allelic series is defined by RFLP. This series correlates to a lesser extent than DQP RFLPs with the HLA-DQ serological specificities. Thus, two DQa RFLPs correlate with a single DQ serotype (DQx la and DQa lc with DQwl), but three DQcc RFLPs correlate with more than one DQ serotype (DQa lb with DQwl and DQw3; DQa2 with DQw2 and DQw3; DQcr3 with DQw2 and DQw3). Individual DQB and DQu RFLP subtypes appear to correlate with single, or associated HLA-DR specificities. Specific combinations of DQB with DQa RFLPs also correlate with HLA-Dw splits of DR2 and DRw6. A system for HLA-DNA typing is described, which uses RFLP patterns generated by sequential hybridization of TuqI-digested DNAs with short DR/?, DQP and DQa cDNA probes. The DQB and DQa probes not only identify the DQ allele, but because of linkage disequilibrium with DR, help to assign the DR allele, which may not always be identified with a DRfi probe alone.
Susceptibility to develop celiac disease is primarily associated with HLA-DQ alleles
Human Immunology, 1990
We have recently reported that the susceptibility to develop celiac disease (CD) seems to be primarily associated to a particular combination of an HLA-DQA1 (DQAI*0501) and an HLA-DQB I (DQB 1 "0201) allele; i.e., a particular DQ ~//3 heterodimer. To investigate whether certain DP alleles might also contribute to the genetic susceptibility, DPAI and DPB1 genes of 94 CD patients and 132 healthy controls were examined by probing in vitro amplified DNA with sequence-specific oligonucleotide probes corresponding to all hitherto known DPA 1 and DPB 1 alleles. The frequencies of the DPAI*0201 and of the DPBI*OIO1 alleles were increased in CD patients compared to healthy controls (0.31 versus 0.14 and 0.25 versus 0.08, respectively). However, these DP alleles were in linkage disequilibrium with CD-associated DQ alleles in the normal population, and the difference in frequency of these DP alleles was no longer significant when CD patients and healthy controls carrying the CD-associated DQAI*0501 and DQB 1"0201 alleles were compared. DQB 1"0201 homozygous individuals were overrepresented among DQBl*O2Ol-positive patients compared to controls. When DQBI*0201 heterozygous patients and controls were compared, nearly identical frequencies of the DPAI*0201 and the DPB I *O I O1 alleles were found. Thus, the observed increase of the DPA I *0201 and DPB I *O l O l alleles among CD patients seems mainly to be caused by linkage disequilibrium to the CDassociated DQ alleles.
European Journal of Immunogenetics, 1994
HLA-DRBI, DQAI and DQBl alleles have been determined in 42 families with one IDDM proband and 64 healthy controls, by oligotyping (PCR-SSO) using primers and probes from the XI International Histocompatibility Workshop. A positive DRB 1 *03 and DRB 1 *04 association with the disease was observed, whereas DRB 1 * 1 1 and DRB 1 *07 showed negative association but 19% of patients carried DRBl alleles different to DRB I *03 or *04. When single alleles were considered, DQA 1 *03 showed the strongest association with susceptibility to the disease (RR = 8.2, Pc = 0.ooOOl) but this association was outgrown by 2 and 3 allele combinations, with genotype DRBI*M-DQA1*03-DQB I *0302/DRB 1 *03-DQA 1 *050 1 -DQB 1 *020 1 showing the strongest association (RR = 28, Pc = 0.002). Application of the relative predispositional effect (RPE) method to our data, revealed a further susceptibility risk provided by the DRB I * 13-DQAI *0102-DQB1*0604 haplotype once DR3 and DR4 haplotypes were removed. When DQAI-DQB I genotypes were analysed for presence of Arg 52 (DQ a) and absence of Asp 57 (DQ p). genotypes S S / S S were found significantly increased in diabetics. Interestingly, one of the strongest associations with the disease was observed with the DQA1*03-DQB 1 *020 1 combination encoded mainly by genes in trans (RR = I 1.7 Pc = 0.00004). These observations and their comparison with DR-DQ haplotypes in more homogeneous ethnic groups support the stronger influence of the DQ molecule rather than the individual DR or DQ alleles in the susceptibility to IDDM. They also emphasize the need for detailed HLA haplotype studies in non-Caucasian and ethnically mixed populations to gain further insight into the nature of genetic and environmental factors contribution to autoimmunity.
Pathology - Research and Practice, 2020
ABCC6, a member of the adenosine 5 0-triphosphate-binding cassette family of genes, encodes multidrug resistance-associated protein 6, a putative transmembrane transporter expressed primarily in the liver and to a significantly lower extent in other tissues. Mutations in ABCC6 result in pseudoxanthoma elasticum, a multisystem heritable connective tissue disorder with variable phenotypic expression. To examine the transcriptional regulation and tissue-specific expression of this gene, we cloned 2.6 kb of human ABCC6 promoter and developed a series of 5 0-deletion constructs linked to luciferase reporter gene. Transient transfections in a number of cultured cell lines of diverse origin identified a specific NF-kB-like sequence (À235/À226), which conferred high level of expression in HepG2 hepatoma cells, inferring liver specificity. The functionality of the promoter fragments was confirmed in vivo by tail vein injection followed by luciferase reporter assay. Testing of selected cytokines revealed that transforming growth factor (TGF)-b upregulated, while tumor necrosis factor (TNF)-a and interferon (IFN)-g downregulated the promoter activity in HepG2 cells. The responsiveness to TGF-b was shown to reside primarily within an Sp1/Sp3 cognate-binding site at À58 to À49. The expression of the ABCC6 promoter was also shown to be markedly enhanced by Sp1 protein, as demonstrated by cotransfection of ABCC6 promoter-luciferase constructs and an Sp1 expression vector in Drosophila SL2 cells, which are devoid of endogenous Sp1. Furthermore, four additional transcription factors, with their cognate-binding sequences present in DNA, were shown to bind the 2.6-kb promoter fragment by protein/DNA array. Collectively, the results indicate that human ABCC6 displays tissue-specific gene expression, which can be modulated by proinflammatory cytokines. These findings may have implications for phenotypic expression of heritable and acquired diseases involving abnormality in the ABCC6 gene.
Determination of DQB1 Alleles Using PCR Amplification and Allele-Specific Primers
European Journal of Immunogenetics, 1995
Molecular genotyping of HLA class I1 genes is commonly carried out using polymerase chain reaction (PCR) in combination with sequence-specific oligotyping (PCR-SSO) or a combination of the PCR and restriction fragment length polymorphism methods (PCR-RFLP). However, the identification of the DQBI type by PCR-SSO and PCR-RFLP is very time-consuming which is disadvantageous for the typing of cadaveric organ donors. We have developed a DQBI typing method using PCR in combination with allele-specific amplification (PCR-ASA), which allows the identification of the 17 most frequent alleles in one step using seven amplification mixtures. PCR allele-specific amplification HLA-DQBI typing is easy to perform, and the results are easy to interpret in routine clinical practice. The PCR-ASA method is therefore better suited to DQBI typing for organ transplantation than other methods.
Human Immunology, 1990
HLA class Il polymorphism is functionally important in the control of immune responses, in transplantation immunology, and in the suceptibility to autoimmune diseases. HLA-DQA1 and -DQB1 genes exhibit a larger degree of allelic polymorphism than usually recognized by routine serology. We have therefore performed an extensive analysis of DQB1 polymorphism by oligotyping. A set of 12 oligo probes was hybridized on polymerase chain reaction-amplified DNA, thus allowing the detection of 12 DQB1 alleles, as demonstrated in homozygous as well as in heterozygous individuals. This highly sensitive detection system is particularly relevant within the DQwl specificity where the 7 allelic sequences can easily be identified. The DQ-DR linkage disequilibrium was analyzed by oligotyping of 80 Caucasoid heterozygous individuals (160 haplotypes), and very tight associations were observed between DRBI and DQB1 alleles. Five DRB1 alleles, DR-BON, DR4/Dw4 or Dwl4, DR7, DRw8.3, and DRwll, however, can be associated with different DQB1 alleles. Moreover the DRB1 and DQB1 oligotyping analysis performed on 20 randomly chosen DRw8 Caucasoid individuals showed a high prevalence of the DRB1 *0801-DQB I *0402 haplotype. By combining the analysis of allelic variations at DRB1, DRB 3, and DQB1 loci, we can detect 33 different DR-DQ combinations in our panel of Caucasoid individuals. We now apply DQB 1 oligotyping on a routine basis for optimal matching of unrelated donors for bone marrow transplantation. ABBREVIATIONS BMT bone marrow transplantation HTC homozygous typing cell PCR polymerase chain reaction RFLP restriction fragment length polymorphism bp base pair IDDM insulin-dependant diabetes mellitus