LACK OF ASSOCIATION BETWEEN POLYMORPHISM OF THE THYROTROPIN RECEPTOR GENE AND GRAVES-DISEASE IN UNITED-KINGDOM AND HONG-KONG CHINESE PATIENTS - CASE-CONTROL AND FAMILY-BASED STUDIES

The thyrotropin receptor (TSH-R) gene is a candidate for genetic susce ptibility to Craves' disease (CD). Previous case control studies inves tigating allelic association of a polymorphism at position 253 (C253 t o A253) of the TSH-R gene have shown conflicting results. We genotyped two independent case control datasets (UK Caucasian and Hong Kong Chi nese), for the A253 polymorphism. The Transmission Disequilibrium Test was also used in a third family-based dataset that included 89 UK Cau casian families (both parents, a GD sibling and an unaffected sibling) . Genotyping was performed by polymerase chain reaction (PCR)-amplific ation of genomic DNA and Tth111 I restriction enzyme digestion. No dif ference in frequencies of the A253 polymorphism between GD (21/204, 10 .3%) and controls (34/358, 9.5%) was found in the UK Caucasians (chi(2 ) = 0.093; p = NS). A similar finding was observed in GD (0/96, 0%) an d controls (2/71, 2.8%) in Hong Kong Chinese subjects (chi(2) = 2.73; p = NS). Results from the 89 UK families showed no deviation from the expected transmission frequency of 0.5, from parents heterozygous for the A253 allele to either Craves' or unaffected offspring (Fisher's ex act test p = 0.22) and, therefore, confirmed a lack of evidence of lin kage disequilibrium between the A253 allele and CD.