DQA2-U ALLELE - A GENETIC-MARKER FOR RELAPSE OF GRAVES-DISEASE

The association of HLA‐DR3 with Graves'disease in Caucasoids is well established but its significance is unclear and its clinical value as a predictive parameter for relapse after a course of antithyroid drug therapy is controversial. We have further investigated the predictive value at the genomic level in 51 patients with Graves'disease who were treated with a 6‐month course of carbimazole and followed up for 2 years. Using DNA‐restriction fragment length polymorphism (DNA‐RFLP) allogenotyping, (i) complete concordance of HLA‐DR assignment was observed between serological and DNA‐RFLP analysis of all but one of 51 patients with Graves'disease; (ii) the DRβ171‐DQα2‐DQβ2a (a DNA‐RFLP allogenotype of the classical Northern European haplotype of HLA‐B8 DR3) was significantly (corrected P = Pcorr <0.02) associated with Graves'disease particularly in patients who relapsed (Pcorr<0.005); (iii) HLA‐DR3 was highly associated with DQA2 U allele (X2=18.53, d.f.2, P< 0.0005); (iv) a strong correlation between the DQA2 U allele and the outcome of the disease was observed. Relapse occurred in 91% (10/11) of the patients who were homozygous for the DQA2 U allele whilst only 65% (15/23) and 41% (7/17) of patients who were hetero or homo‐zygous for the DQA2 L allele (DQA2 U/L and DQA2 L/L) relapsed within the same period of follow‐up (X2= 7.18, d.f.2, P< 0.05). Though the relapse rate in patients with the DQA2 U/U genotype was not significantly higher than the relapse rate in patients with the DQA2 U/L genotype, it was significantly higher than the relapse rate in patients with DQA2 L/L genotype (P< 0.0001) with a relative risk of 14.3. Copyright © 1990, Wiley Blackwell. All rights reserved