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Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac patients of Southern Europe.
Tissue Antigens. 2008 Mar; 71(3):213-8.TA

Abstract

The DQ2 heterodimer, encoded by the human leukocyte antigen (HLA)-DQA1*05-DQB1*02 alleles, is the major genetic susceptibility factor for celiac disease (CD). However, the risk associated to HLA alleles varies among populations. While DRB1*03 is almost the only CD susceptibility allele in Northern Europe with a homozygote frequency of around 30%, CD in south European countries is also associated with the DRB1*07, and DRB1*03 homozygotes patients are rare. Some authors have suggested that DQB1*02-DRB1*03/DQB1*02-DRB1*03 and DQB1*02-DRB1*03/DQB1*02-DRB1*07 may confer different risk susceptibility to CD. This hypothesis, however, has not been demonstrated in a recent family-based study carried out in Finland, suggesting that the proposed differences in risk may be secondary to stratification burdens of case-control studies. To assess this issue, we have investigated the effect of different haplotypes carried trans to DQB1*02-DRB1*03 as additional factors for CD in Spain, using two statistical approaches, a case-control study and a family-based study. We found that DQB1*02-DRB1*03/DQB1*02-DRB1*03 and DQB1*02-DRB1*03/DQB1*02-DRB1*07 were the only combinations that showed a strong and independent association to CD. We did not observe any difference in susceptibility risk conferred by DQB1*02-DRB1*03 and DQB1*02-DRB1*07 when carried trans to DQB1*02-DRB1*03, suggesting that variation in HLA haplotype frequencies among populations may not represent real differences in risk to CD development. We also confirmed a gene dosage effect of the DQB1*02-DRB1*03 haplotype estimating that DQB1*02 homozygotes are at fivefold increased risk for CD compared with DQB1*02 heterozygotes. This risk is conferred by the second copy of the DQB1*02 allele and it seems to be independent of the DQA1.

Authors+Show Affiliations

Department of Genetics, Hospital Virgen del Camino, Navarra, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18257894

Citation

Hernández-Charro, B, et al. "Modifying Effect of HLA Haplotypes Located Trans to DQB1*02-DRB1*03 in Celiac Patients of Southern Europe." Tissue Antigens, vol. 71, no. 3, 2008, pp. 213-8.
Hernández-Charro B, Donat E, Miner I, et al. Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac patients of Southern Europe. Tissue Antigens. 2008;71(3):213-8.
Hernández-Charro, B., Donat, E., Miner, I., Aranburu, E., Sánchez-Valverde, F., & Ramos-Arroyo, M. A. (2008). Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac patients of Southern Europe. Tissue Antigens, 71(3), 213-8. https://doi.org/10.1111/j.1399-0039.2007.01003.x
Hernández-Charro B, et al. Modifying Effect of HLA Haplotypes Located Trans to DQB1*02-DRB1*03 in Celiac Patients of Southern Europe. Tissue Antigens. 2008;71(3):213-8. PubMed PMID: 18257894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac patients of Southern Europe. AU - Hernández-Charro,B, AU - Donat,E, AU - Miner,I, AU - Aranburu,E, AU - Sánchez-Valverde,F, AU - Ramos-Arroyo,M A, PY - 2008/2/9/pubmed PY - 2008/5/3/medline PY - 2008/2/9/entrez SP - 213 EP - 8 JF - Tissue antigens JO - Tissue Antigens VL - 71 IS - 3 N2 - The DQ2 heterodimer, encoded by the human leukocyte antigen (HLA)-DQA1*05-DQB1*02 alleles, is the major genetic susceptibility factor for celiac disease (CD). However, the risk associated to HLA alleles varies among populations. While DRB1*03 is almost the only CD susceptibility allele in Northern Europe with a homozygote frequency of around 30%, CD in south European countries is also associated with the DRB1*07, and DRB1*03 homozygotes patients are rare. Some authors have suggested that DQB1*02-DRB1*03/DQB1*02-DRB1*03 and DQB1*02-DRB1*03/DQB1*02-DRB1*07 may confer different risk susceptibility to CD. This hypothesis, however, has not been demonstrated in a recent family-based study carried out in Finland, suggesting that the proposed differences in risk may be secondary to stratification burdens of case-control studies. To assess this issue, we have investigated the effect of different haplotypes carried trans to DQB1*02-DRB1*03 as additional factors for CD in Spain, using two statistical approaches, a case-control study and a family-based study. We found that DQB1*02-DRB1*03/DQB1*02-DRB1*03 and DQB1*02-DRB1*03/DQB1*02-DRB1*07 were the only combinations that showed a strong and independent association to CD. We did not observe any difference in susceptibility risk conferred by DQB1*02-DRB1*03 and DQB1*02-DRB1*07 when carried trans to DQB1*02-DRB1*03, suggesting that variation in HLA haplotype frequencies among populations may not represent real differences in risk to CD development. We also confirmed a gene dosage effect of the DQB1*02-DRB1*03 haplotype estimating that DQB1*02 homozygotes are at fivefold increased risk for CD compared with DQB1*02 heterozygotes. This risk is conferred by the second copy of the DQB1*02 allele and it seems to be independent of the DQA1. SN - 0001-2815 UR - https://www.unboundmedicine.com/medline/citation/18257894/Modifying_effect_of_HLA_haplotypes_located_trans_to_DQB1_02_DRB1_03_in_celiac_patients_of_Southern_Europe_ L2 - https://doi.org/10.1111/j.1399-0039.2007.01003.x DB - PRIME DP - Unbound Medicine ER -