PMID- 2893373
OWN - NLM
STAT- MEDLINE
DCOM- 19880302
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 85
IP  - 1
DP  - 1988 Jan
TI  - An extended HLA-D region haplotype associated with celiac disease.
PG  - 222-6
AB  - Celiac disease has one of the strongest associations with HLA (human leukocyte 
      antigen) class II markers of the known HLA-linked diseases. This association is 
      primarily with the class II serologic specificities HLA-DR3 and -DQw2. We 
      previously described a restriction fragment length polymorphism (RFLP) 
      characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an 
      HLA class II beta-chain gene, which distinguishes the class II HLA haplotype of 
      celiac disease patients from those of many serologically matched controls. We now 
      report the isolation of this beta-chain gene from a bacteriophage genomic library 
      constructed from the DNA of a celiac disease patient. Based on restriction 
      mapping and differential hybridization with class II cDNA and oligonucleotide 
      probes, this gene was identified as one encoding an HLA-DP beta chain. This 
      celiac disease-associated HLA-DP beta-chain gene was flanked by HLA-DP 
      alpha-chain genes and, therefore, was probably in its normal chromosomal 
      location. The HLA-DP alpha-chain genes of celiac disease patients also were 
      studied by RFLP analysis; 84% of HLA-DR3, -DQw2 patients had a 16-kb Xba I 
      fragment that was present in only 36% of HLA-DR3, -DQw2 controls. Moreover, 79% 
      of these patients had both alpha- and beta-chain polymorphisms in contrast to 27% 
      of controls. Thus, celiac disease is associated with a subset of HLA-DR3, -DQw2 
      haplotypes characterized by HLA-DP alpha- and beta-chain gene RFLPs. Within the 
      celiac-disease patient population, the joint segregation of these HLA-DP genes 
      with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) 
      that the class II HLA haplotype associated with celiac disease is extended 
      throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility 
      genes may reside as far centromeric on this haplotype as the HLA-DP subregion.
FAU - Howell, M D
AU  - Howell MD
AD  - Department of Medicine, University of California, San Diego, La Jolla 92093.
FAU - Smith, J R
AU  - Smith JR
FAU - Austin, R K
AU  - Austin RK
FAU - Kelleher, D
AU  - Kelleher D
FAU - Nepom, G T
AU  - Nepom GT
FAU - Volk, B
AU  - Volk B
FAU - Kagnoff, M F
AU  - Kagnoff MF
LA  - eng
GR  - DK-35108/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (HLA-D Antigens)
RN  - 0 (Macromolecular Substances)
RN  - 9007-49-2 (DNA)
RN  - EC 3.1.21.- (DNA Restriction Enzymes)
SB  - IM
MH  - B-Lymphocytes/immunology
MH  - Celiac Disease/genetics/*immunology
MH  - DNA/genetics
MH  - DNA Restriction Enzymes
MH  - HLA-D Antigens/*genetics
MH  - *Haplotypes
MH  - Humans
MH  - Macromolecular Substances
MH  - *Major Histocompatibility Complex
MH  - Nucleic Acid Hybridization
MH  - Polymorphism, Restriction Fragment Length
MH  - Reference Values
PMC - PMC279516
EDAT- 1988/01/01 00:00
MHDA- 1988/01/01 00:01
PMCR- 1988/07/01
CRDT- 1988/01/01 00:00
PHST- 1988/01/01 00:00 [pubmed]
PHST- 1988/01/01 00:01 [medline]
PHST- 1988/01/01 00:00 [entrez]
PHST- 1988/07/01 00:00 [pmc-release]
AID - 10.1073/pnas.85.1.222 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1988 Jan;85(1):222-6. doi: 10.1073/pnas.85.1.222.