THE BGL-II RFLP ASSOCIATED WITH TYPE-1 DIABETES IN DR3-POSITIVE SUBJECTS IS NOT DUE TO A DQA1 PROMOTER REGION POLYMORPHISM

Type 1 (insulin-dependent) diabetes is strongly associated with the HL A genes encoding DR3 and DR4 and their associated DQ alleles. While 70 % of all Caucasian diabetic patients carry the DR3-associated allele D QA1()0501, this allele also occurs in up to 40% of the healthy popula tion. A DQA1 Bgl II 7.2 kb RFLP has been shown to identify a disease-a ssociated subset of DR3-positive subjects. We examined the frequency o f this RFLP pattern in 43 diabetic and 25 control DR3-positive subject s and found it to be present in 27 (65%) and 5 (20%) respectively(p = 0.0012). The promoter of the DR3-associated DQA1()0501 allele was amp lified in four diabetic subjects who were positive, and four control s ubjects who were negative, for the 7.2 kb band. The promoter was diges ted with Bgl II to determine whether polymorphism within the promoter created a disease-associated Bgl II restriction site, which might infl uence disease susceptibility by an effect on gene transcription. No am plified promoter fragment contained a Bgl II restriction site, suggest ing that the disease-associated 7.2 kb band does not result from DQA1 promoter region polymorphism but may be due to polymorphism elsewhere on the DR3 haplotype.