Polymorphisms of the HLA-DP region loci have been shown to associate with autoimmune diseases which share immunological features with IgAN; coeliac disease (CD) and dermatitis herpetiformis (DH).
The linkage of the DPB1*0101 allele with the DQ locus and the observation that the DP but not the DQ association appears to be ethnically dependent strongly support a secondary role of DP molecules in celiac disease susceptibility.
Of CD patients, 92% (50% DR3 and 42% DR5,7) compared to 18% of the controls carry both DQA1*0501 and DQB1*0201 alleles, so that the combination confers an RR of 52, higher than both the risks of the single alleles (DQA1*0501 RR = 19, DQB1*0201 RR = 30), confirming the primary role of the dimer in determining genetic predisposition to CD both in DR3 and in DR5,7 subjects.
A possible involvement of the PSF1 and PSF2 genes in susceptibility to MHC-associated diseases was examined in a preliminary assessment in patients with ankylosing spondylitis, insulin-dependent diabetes mellitus, or celiac disease.
A possible involvement of the PSF1 and PSF2 genes in susceptibility to MHC-associated diseases was examined in a preliminary assessment in patients with ankylosing spondylitis, insulin-dependent diabetes mellitus, or celiac disease.
However other genetic factors are probably relevant, since about 10% of the patients with DH and CD lack the DQA1*0501/B1*0201 heterodimer while the majority of individuals presenting this genotype and also being exposed to gluten diets did not suffer from these diseases.
The observation that coeliac children negative for DR3 and DR7 showed lower AGA levels is consistent with clinical and genetic heterogeneity of coeliac disease.
In dermatitis herpetiformis, as in celiac disease, the strongest association of disease was with the DQ subregion alleles DQB1*0201 and DQA1*0501 that are linked to the DRB1*0301 allele.
Further, they indicate that a specific DQ molecule, when present in combination with the product of one of several different DPB1 alleles, may contribute to susceptibility to the intestinal lesion, which is common to dermatitis herpetiformis and celiac disease.
In dermatitis herpetiformis, as in celiac disease, the strongest association of disease was with the DQ subregion alleles DQB1*0201 and DQA1*0501 that are linked to the DRB1*0301 allele.
In dermatitis herpetiformis, as in celiac disease, the strongest association of disease was with the DQ subregion alleles DQB1*0201 and DQA1*0501 that are linked to the DRB1*0301 allele.
Msp I DP beta polymorphism was studied in 52 healthy subjects and 59 patients: a 4.9 kb fragment was present in 51% of patients with coeliac disease compared to 11.5% of control subjects (p less than 0.001).
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.
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.
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.
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.
Furthermore, the increased frequency of the 4.0-kilobase Rsa I DP B gene restriction fragment length polymorphism in celiac disease can be accounted for by the overrepresentation in disease of the alleles DPB1 and DPB3.