SUSCEPTIBILITY TO AUTOIMMUNE-THYROIDITIS IN DOWNS-SYNDROME IS ASSOCIATED WITH THE MAJOR HISTOCOMPATIBILITY CLASS-II DQA-0301 ALLELE

OBJECTIVE Abnormalities of immune function, including thyroid autoimmu nity, are common features of Down's syndrome, and the genetic associat ions of autoimmune thyroiditis have been extensively studied in otherw ise normal patients with thyroid disease. In this study we have examin ed the HLA associations of autoimmune thyroid diseases in a cohort of adult subjects with Down's syndrome, to see whether they differed from those found in other populations. DESIGN AND MEASUREMENTS Restriction fragment length polymorphism analysis was carried out in 41 subjects whose thyroid status was assessed by measuring thyroid function and au toantibody titres. The genotypes of subjects with and without hypothyr oid autoimmune diseases were compared. SUBJECTS Forty-one older subjec t's with Down's syndrome and an average age of 46.6 years under review by the Maudsley Hospital. RESULTS Hypothyroid autoimmune disease in t his study group was clearly associated with a 5.5-kb Taq1 DQA restrict ion fragment length polymorphism (P-c = 0.013) corresponding to the ma jor histocompatibility (MHC) class II DQA 0301 allele. CONCLUSIONS In contrast to Hashimoto's thyroiditis and atrophic thyroiditis, there is a strong association between class II genotypes and hypothyroid autoi mmune disease in Down's syndrome. This implies a role for a gene or ge nes on chromosome 21 in the development of autoimmune thyroid disease.