NORMAL FUNCTION IN-VIVO OF A HOMOZYGOTIC POLYMORPHISM IN THE HUMAN THYROTROPIN RECEPTOR

We have demonstrated previously an association between a polymorphism in the human thyrotropin receptor gene and an increased prevalence of autoimmune thyroid disease in individuals bearing this polymorphic all ele, The polymorphism involves the nucleotide base substitution of a c ytosine for the wild-type adenine at the first position of codon 52 an d is found generally in the heterozygotic state, Such a change results in the substitution of a threonine for the wild-type proline at this position in the receptor protein sequence, The resulting protein would lack a beta turn (at position 52) in a potential loop conformation, a nd thus would have a significantly altered three-dimensional conformat ion, The biologic consequences of this conformational change in the re ceptor are unknown, but may involve altered function or immunogenicity , We report here two individuals with normal thyroid function who are homozygous for the thyrotropin receptor polymorphism, suggesting that the altered receptor is able to respond normally to thyrotropin with r espect to the maintenance of the euthyroid state.