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DQA2 U ALLELE: A GENETIC MARKER FOR RELAPSE OF Graves'DISEASE
Author(s) -
RATANACHAIYAVONG SUVINA,
GUNN CATHERINE A.,
BIDWELL ELIZABETH A.,
DARKE C.,
HALL R.,
McGREGOR A. M.
Publication year - 1990
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1990.tb00860.x
Subject(s) - graves' disease , allele , medicine , carbimazole , restriction fragment length polymorphism , gastroenterology , human leukocyte antigen , endocrinology , immunology , biology , disease , genetics , genotype , antigen , gene
SUMMARY 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 DRβ17 1 ‐DQα2‐DQβ2a (a DNA‐RFLP allogenotype of the classical Northern European haplotype of HLA‐B8 DR3) was significantly (corrected P = P corr <0.02) associated with Graves'disease particularly in patients who relapsed (P corr <0.005); (iii) HLA‐DR3 was highly associated with DQA2 U allele (X 2 =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 (X 2 = 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.