Susceptibility to develop celiac disease is primarily associated with HLA-DQ alleles.
We have recently reported that the susceptibility to develop celiac disease (CD) seems to be primarily associated to a particular combination of an HLA-DQA1 (DQA1*0501) and an HLA-DQB1 (DQB1*0201) allele: i.e., a particular DQ alpha/beta heterodimer. To investigate whether certain DP alleles might also contribute to the genetic susceptibility, DPA1 and DPB1 genes of 94 CD patients and 132 healthy controls were examined by probing in vitro amplified DNA with sequence-specific oligonucleotide probes corresponding to all hitherto known DPA1 and DPB1 alleles. The frequencies of the DPA1*0201 and of the DPB1*0101 alleles were increased in CD patients compared to healthy controls (0.31 versus 0.14 and 0.25 versus 0.08, respectively). However, these DP alleles were in linkage disequilibrium with CD-associated DQ alleles in the normal population, and the difference in frequency of these DP alleles was no longer significant when CD patients and healthy controls carrying the CD-associated DQA1*0501 and DQB1*0201 alleles were compared. DQB1*0201 homozygous individuals were overrepresented among DQB1*0201-positive patients compared to controls. When DQB1*0201 heterozygous patients and controls were compared, nearly identical frequencies of the DPA1*0201 and the DPB1*0101 alleles were found. Thus, the observed increase of the DPA1*0201 and DPB1*0101 alleles among CD patients seems mainly to be caused by linkage disequilibrium to the CD-associated DQ alleles.
Spurkland
A
A
Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
Sollid
L M
LM
Rønningen
K S
KS
Bosnes
V
V
Ek
J
J
Vartdal
F
F
Thorsby
E
E
D000483:Alleles; D001483:Base Sequence; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology*; D004247:DNA; D004198:Disease Susceptibility; D005784:Gene Amplification; D006682:HLA-DP Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012150:Polymorphism, Restriction Fragment Length; D011897:Random Allocation
D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D015345:Oligonucleotide Probes; D004247:DNA