PMID- 18257894
OWN - NLM
STAT- MEDLINE
DCOM- 20080502
LR  - 20111117
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 71
IP  - 3
DP  - 2008 Mar
TI  - Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac 
      patients of Southern Europe.
PG  - 213-8
LID - 10.1111/j.1399-0039.2007.01003.x [doi]
AB  - 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.
FAU - Hernandez-Charro, B
AU  - Hernandez-Charro B
AD  - Department of Genetics, Hospital Virgen del Camino, Navarra, Spain.
FAU - Donat, E
AU  - Donat E
FAU - Miner, I
AU  - Miner I
FAU - Aranburu, E
AU  - Aranburu E
FAU - Sanchez-Valverde, F
AU  - Sanchez-Valverde F
FAU - Ramos-Arroyo, M A
AU  - Ramos-Arroyo MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Case-Control Studies
MH  - Celiac Disease/*genetics/*immunology
MH  - Female
MH  - Gene Dosage
MH  - Gene Frequency
MH  - Genetic Complementation Test
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Haplotypes
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Male
MH  - Risk Factors
MH  - Spain
EDAT- 2008/02/09 09:00
MHDA- 2008/05/03 09:00
CRDT- 2008/02/09 09:00
PHST- 2008/02/09 09:00 [pubmed]
PHST- 2008/05/03 09:00 [medline]
PHST- 2008/02/09 09:00 [entrez]
AID - TAN1003 [pii]
AID - 10.1111/j.1399-0039.2007.01003.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2008 Mar;71(3):213-8. doi: 10.1111/j.1399-0039.2007.01003.x.