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Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients.
Genes Immun. 2004 May; 5(3):215-20.GI

Abstract

The major genetic susceptibility to coeliac disease is contributed by the human leukocyte antigen (HLA) region. The primary association is with the HLA-DQ2 molecule, encoded by the DQA1*05 and DQB1*02 alleles, which is expressed by over 90% of patients. The aim of our study was to perform an extensive scan of the entire HLA region to determine whether there is evidence for the presence of additional HLA susceptibility genes for coeliac disease in the Dutch population, acting independently of DQ2. In all, 16 microsatellite markers and the DQA1 and DQB1 genes were genotyped in simplex cis DQ2-positive coeliac disease families and cis DQ2-positive control families. Allele frequencies of markers on phase-known DQ2-positive haplotypes transmitted to patients were compared to a combined group of DQ2-positive nontransmitted and control haplotypes, thereby controlling for the DQ2 contribution. No significant differences at any of the marker loci were detected, suggesting that DQ2 is the major HLA risk factor for coeliac disease. Individuals homozygous for DQ2 or heterozygous for DQA1*05-DQB1*02/DQA1*0201-DQB1*02 were found to be at five-fold increased risk for development of coeliac disease (P<10(-8)). This risk seems to be conferred by the presence of a second DQB1*02 allele next to one DQA1*05-DQB1*02 haplotype, independently of the second DQA1 allele.

Authors+Show Affiliations

Complex Genetics Group, Department of Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15014431

Citation

van Belzen, M J., et al. "Defining the Contribution of the HLA Region to Cis DQ2-positive Coeliac Disease Patients." Genes and Immunity, vol. 5, no. 3, 2004, pp. 215-20.
van Belzen MJ, Koeleman BP, Crusius JB, et al. Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients. Genes Immun. 2004;5(3):215-20.
van Belzen, M. J., Koeleman, B. P., Crusius, J. B., Meijer, J. W., Bardoel, A. F., Pearson, P. L., Sandkuijl, L. A., Houwen, R. H., & Wijmenga, C. (2004). Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients. Genes and Immunity, 5(3), 215-20.
van Belzen MJ, et al. Defining the Contribution of the HLA Region to Cis DQ2-positive Coeliac Disease Patients. Genes Immun. 2004;5(3):215-20. PubMed PMID: 15014431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients. AU - van Belzen,M J, AU - Koeleman,B P C, AU - Crusius,J B A, AU - Meijer,J W R, AU - Bardoel,A F J, AU - Pearson,P L, AU - Sandkuijl,L A, AU - Houwen,R H J, AU - Wijmenga,C, PY - 2004/3/12/pubmed PY - 2004/11/9/medline PY - 2004/3/12/entrez SP - 215 EP - 20 JF - Genes and immunity JO - Genes Immun. VL - 5 IS - 3 N2 - The major genetic susceptibility to coeliac disease is contributed by the human leukocyte antigen (HLA) region. The primary association is with the HLA-DQ2 molecule, encoded by the DQA1*05 and DQB1*02 alleles, which is expressed by over 90% of patients. The aim of our study was to perform an extensive scan of the entire HLA region to determine whether there is evidence for the presence of additional HLA susceptibility genes for coeliac disease in the Dutch population, acting independently of DQ2. In all, 16 microsatellite markers and the DQA1 and DQB1 genes were genotyped in simplex cis DQ2-positive coeliac disease families and cis DQ2-positive control families. Allele frequencies of markers on phase-known DQ2-positive haplotypes transmitted to patients were compared to a combined group of DQ2-positive nontransmitted and control haplotypes, thereby controlling for the DQ2 contribution. No significant differences at any of the marker loci were detected, suggesting that DQ2 is the major HLA risk factor for coeliac disease. Individuals homozygous for DQ2 or heterozygous for DQA1*05-DQB1*02/DQA1*0201-DQB1*02 were found to be at five-fold increased risk for development of coeliac disease (P<10(-8)). This risk seems to be conferred by the presence of a second DQB1*02 allele next to one DQA1*05-DQB1*02 haplotype, independently of the second DQA1 allele. SN - 1466-4879 UR - https://www.unboundmedicine.com/medline/citation/15014431/Defining_the_contribution_of_the_HLA_region_to_cis_DQ2_positive_coeliac_disease_patients_ L2 - http://dx.doi.org/10.1038/sj.gene.6364061 DB - PRIME DP - Unbound Medicine ER -