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We investigated polymorphism of HLA-DP genes in three DR3 related diseases, confirming an association of coeliac disease with a Bgl II DPa polymorphism (a restriction fragment sized 3*5 kb present in 75% of patients compared to 34% of control subjects, p<0001), and finding a weaker association with dermatitis herpetiformis (57% v 34%, p=001) and no association with insulin dependent diabetes mellitus. The association with coeliac disease was further investigated. Msp I DPf3 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<0001). Furthermore, nearly all subjects with the DPa 3.5 kb fragment also had the DP, 4*9 kb fragment. However, disease frequency was still increased in the DPa 3.5 positive/DPP 4-9 negative group.In seven families, each with at least two affected members, while the DPa 3.5 fragment was frequently present in patients it did not preferentially segregate with any particular HLA haplotype -for example, those associated with DR3 or DR7 -and therefore is not part of an extended haplotype associated with coeliac disease. We therefore conclude that a gene(s) in the HLA-DP region predisposes to coeliac disease independently of the HLA-DRIDQ regions.

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