title: A polymorphism in the extracellular domain of the thyrotropin receptor is highly associated with autoimmune thyroid disease in females.
abstract: We and others have described previously a polymorphism at the first position of codon 52 (C52 --> A52) of the human thyrotropin receptor (hTSHr) gene. To determine its potential significance, we studied female (n = 100) and male (n = 25) patients with autoimmune thyroid disease (Graves' disease, n = 91; Hashimoto's thyroiditis, n = 34) and normal individuals [n = 121, female (n = 69), male (n = 52)]. Screening was performed using AciI restriction enzyme digestions of PCR-amplified genomic DNA. All codon 52 polymorphisms were verified by direct DNA sequencing. Data were analyzed using Chi-square or Fisher exact tests and p-values were corrected for multiple comparisons. Our studies demonstrated that this polymorphism is highly associated with autoimmune thyroid disease in the female population (corrected p = 0.008). We found no such association in the male population. Within females, there was a greater association between Graves' disease and the polymorphism (corrected p = 0.017) than between Hashimoto's thyroiditis and the polymorphism (corrected p = 0.090). The polymorphism was present in a higher proportion of Graves' disease patients with Graves' ophthalmopathy and pretibial dermopathy (40%) or Graves' ophthalmopathy, pretibial dermopathy, and acropachy (60%), than in patients with Graves' disease alone (15%), or Graves' disease and Graves' ophthalmopathy alone (17%). In conclusion, a polymorphism (C52 --> A52) of the hTSHr is associated with autoimmune thyroid disease in females.
authors.affiliation: Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Cuddihy
authors.forename: C M
authors.initials: CM
authors.lastname: Dutton
authors.forename: R S
authors.initials: RS
authors.lastname: Bahn
mesh_terms: D001483:Base Sequence; D003062:Codon; D004247:DNA / Q000302:isolation & purification; D004262:DNA Restriction Enzymes; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006111:Graves Disease / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012313:RNA / Q000032:analysis; D011989:Receptors, Thyrotropin / Q000235:genetics* / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; D011989:Receptors, Thyrotropin; D012313:RNA; D004247:DNA; D004262:DNA Restriction Enzymes