POLYMORPHISM OF THE 5’ FLANKING REGION OF THE HLA‐DQA1 GENE IN COELIAC DISEASE

M. de la Paz Bettinotti, A. Kolek, G. Brünnler, P. Haas, C. Paul, M. Hochberger, A. Bartova, A. Kimura, T. Sasazuki, E. D. Albert

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Abstract

Coeliac disease (CD) is associated with particular HLA genotypes. The susceptibility gene (or genes) has been mapped to the class II region, most probably to the DQ loci. Polymorphism of the upstream promoter region of the DQA1 gene (QAP) has been recently reported. At least ten variants or QAP alleles have been found, some of which are present in the as‐acting regulatory sequences. Allelic differences in DQ molecule expression may play a role in susceptibility to CD. We investigated the QAP polymorphism in 102 CD patients and 142 unrelated healthy controls of Czech origin using polymerase chain reaction amplification (PCR) of genomic DNA and oligonucleotide probes. We found a significant frequency increase of the alleles QAP 4.1 (RR = 10.3, p.c. = 10‐6) and QAP 2.1 (RR = 2.4, p.c. = 0.017) in patients over controls. An increased susceptibility is provided by the presence of both alleles, as is shown by the higher proportion of QAP 4.1, 2.1 heterozygotes among patients than expected from the Hardy‐Weinberg equilibrium and by the comparison of the odds ratios for these alleles. There is a strong linkage disequilibrium between the QAP alleles and the DQA1, DQB1, and DRB1 loci. Two haplotypes carrying the QAP alleles whose frequency is increased are predominant in this group of CD patients: DQB1* 0201, DQA1* 0501, QAP 4.1, DRB1* 0301 and DQB1* 0201, DQA1* 0201, QAP 2.1, DRB1* 0701. Thus, the QAP variants are increased as part of these haplotypes and we cannot discriminate if they are responsible for the primary association.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalInternational Journal of Immunogenetics
Volume20
Issue number5
DOIs
Publication statusPublished - Oct 1993

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5' Flanking Region
Celiac Disease
Alleles
Gene Frequency
Haplotypes
Genes
Oligonucleotide Probes
Linkage Disequilibrium
DNA Probes
Heterozygote
Genetic Promoter Regions
Odds Ratio
Genotype
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

de la Paz Bettinotti, M., Kolek, A., Brünnler, G., Haas, P., Paul, C., Hochberger, M., ... Albert, E. D. (1993). POLYMORPHISM OF THE 5’ FLANKING REGION OF THE HLA‐DQA1 GENE IN COELIAC DISEASE. International Journal of Immunogenetics, 20(5), 399-407. https://doi.org/10.1111/j.1744-313X.1993.tb00159.x

POLYMORPHISM OF THE 5’ FLANKING REGION OF THE HLA‐DQA1 GENE IN COELIAC DISEASE. / de la Paz Bettinotti, M.; Kolek, A.; Brünnler, G.; Haas, P.; Paul, C.; Hochberger, M.; Bartova, A.; Kimura, A.; Sasazuki, T.; Albert, E. D.

In: International Journal of Immunogenetics, Vol. 20, No. 5, 10.1993, p. 399-407.

Research output: Contribution to journalArticle

de la Paz Bettinotti, M, Kolek, A, Brünnler, G, Haas, P, Paul, C, Hochberger, M, Bartova, A, Kimura, A, Sasazuki, T & Albert, ED 1993, 'POLYMORPHISM OF THE 5’ FLANKING REGION OF THE HLA‐DQA1 GENE IN COELIAC DISEASE', International Journal of Immunogenetics, vol. 20, no. 5, pp. 399-407. https://doi.org/10.1111/j.1744-313X.1993.tb00159.x
de la Paz Bettinotti, M. ; Kolek, A. ; Brünnler, G. ; Haas, P. ; Paul, C. ; Hochberger, M. ; Bartova, A. ; Kimura, A. ; Sasazuki, T. ; Albert, E. D. / POLYMORPHISM OF THE 5’ FLANKING REGION OF THE HLA‐DQA1 GENE IN COELIAC DISEASE. In: International Journal of Immunogenetics. 1993 ; Vol. 20, No. 5. pp. 399-407.
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abstract = "Coeliac disease (CD) is associated with particular HLA genotypes. The susceptibility gene (or genes) has been mapped to the class II region, most probably to the DQ loci. Polymorphism of the upstream promoter region of the DQA1 gene (QAP) has been recently reported. At least ten variants or QAP alleles have been found, some of which are present in the as‐acting regulatory sequences. Allelic differences in DQ molecule expression may play a role in susceptibility to CD. We investigated the QAP polymorphism in 102 CD patients and 142 unrelated healthy controls of Czech origin using polymerase chain reaction amplification (PCR) of genomic DNA and oligonucleotide probes. We found a significant frequency increase of the alleles QAP 4.1 (RR = 10.3, p.c. = 10‐6) and QAP 2.1 (RR = 2.4, p.c. = 0.017) in patients over controls. An increased susceptibility is provided by the presence of both alleles, as is shown by the higher proportion of QAP 4.1, 2.1 heterozygotes among patients than expected from the Hardy‐Weinberg equilibrium and by the comparison of the odds ratios for these alleles. There is a strong linkage disequilibrium between the QAP alleles and the DQA1, DQB1, and DRB1 loci. Two haplotypes carrying the QAP alleles whose frequency is increased are predominant in this group of CD patients: DQB1* 0201, DQA1* 0501, QAP 4.1, DRB1* 0301 and DQB1* 0201, DQA1* 0201, QAP 2.1, DRB1* 0701. Thus, the QAP variants are increased as part of these haplotypes and we cannot discriminate if they are responsible for the primary association.",
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AU - de la Paz Bettinotti, M.

AU - Kolek, A.

AU - Brünnler, G.

AU - Haas, P.

AU - Paul, C.

AU - Hochberger, M.

AU - Bartova, A.

AU - Kimura, A.

AU - Sasazuki, T.

AU - Albert, E. D.

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N2 - Coeliac disease (CD) is associated with particular HLA genotypes. The susceptibility gene (or genes) has been mapped to the class II region, most probably to the DQ loci. Polymorphism of the upstream promoter region of the DQA1 gene (QAP) has been recently reported. At least ten variants or QAP alleles have been found, some of which are present in the as‐acting regulatory sequences. Allelic differences in DQ molecule expression may play a role in susceptibility to CD. We investigated the QAP polymorphism in 102 CD patients and 142 unrelated healthy controls of Czech origin using polymerase chain reaction amplification (PCR) of genomic DNA and oligonucleotide probes. We found a significant frequency increase of the alleles QAP 4.1 (RR = 10.3, p.c. = 10‐6) and QAP 2.1 (RR = 2.4, p.c. = 0.017) in patients over controls. An increased susceptibility is provided by the presence of both alleles, as is shown by the higher proportion of QAP 4.1, 2.1 heterozygotes among patients than expected from the Hardy‐Weinberg equilibrium and by the comparison of the odds ratios for these alleles. There is a strong linkage disequilibrium between the QAP alleles and the DQA1, DQB1, and DRB1 loci. Two haplotypes carrying the QAP alleles whose frequency is increased are predominant in this group of CD patients: DQB1* 0201, DQA1* 0501, QAP 4.1, DRB1* 0301 and DQB1* 0201, DQA1* 0201, QAP 2.1, DRB1* 0701. Thus, the QAP variants are increased as part of these haplotypes and we cannot discriminate if they are responsible for the primary association.

AB - Coeliac disease (CD) is associated with particular HLA genotypes. The susceptibility gene (or genes) has been mapped to the class II region, most probably to the DQ loci. Polymorphism of the upstream promoter region of the DQA1 gene (QAP) has been recently reported. At least ten variants or QAP alleles have been found, some of which are present in the as‐acting regulatory sequences. Allelic differences in DQ molecule expression may play a role in susceptibility to CD. We investigated the QAP polymorphism in 102 CD patients and 142 unrelated healthy controls of Czech origin using polymerase chain reaction amplification (PCR) of genomic DNA and oligonucleotide probes. We found a significant frequency increase of the alleles QAP 4.1 (RR = 10.3, p.c. = 10‐6) and QAP 2.1 (RR = 2.4, p.c. = 0.017) in patients over controls. An increased susceptibility is provided by the presence of both alleles, as is shown by the higher proportion of QAP 4.1, 2.1 heterozygotes among patients than expected from the Hardy‐Weinberg equilibrium and by the comparison of the odds ratios for these alleles. There is a strong linkage disequilibrium between the QAP alleles and the DQA1, DQB1, and DRB1 loci. Two haplotypes carrying the QAP alleles whose frequency is increased are predominant in this group of CD patients: DQB1* 0201, DQA1* 0501, QAP 4.1, DRB1* 0301 and DQB1* 0201, DQA1* 0201, QAP 2.1, DRB1* 0701. Thus, the QAP variants are increased as part of these haplotypes and we cannot discriminate if they are responsible for the primary association.

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