title: Association of the UGT1A1-53(TA)n polymorphism with L-thyroxine doses required for thyrotropin suppression in patients with differentiated thyroid cancer.
abstract: There is a considerable interindividual variation in L-thyroxine [3,5,3',5'-tetraiodo-l-thyronine (T4)] dose required for thyrotropin (thyroid-stimulating hormone) suppression in patients with differentiated thyroid cancer. To investigate whether uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)-mediated T4 glucuronidation in liver affects T4 dose, we genotyped 101 patients for the common UGT1A1-53(TA)n polymorphism and compared T4 doses among patients having zero (5/6 and 6/6 genotypes), one (6/7 genotype), or two (7/7 and 7/8 genotypes) copies of the low-expression (TA)7 and (TA)8 alleles. A significant trend for decreasing T4 dose with increasing number of copies of (TA)7 and (TA)8 (P=0.037) and significant difference in T4 dose across the UGT1A1-53(TA)n genotypes (P=0.048) were observed, despite considerable overlap of T4 doses among different genotypes. These results are consistent with reduced T4 glucuronidation in patients with low-expression (TA)7 and (TA)8 alleles and provide the first evidence for association between UGT1A1-53(TA)n and T4-dose requirement for thyroid-stimulating hormone suppression in a natural clinical setting.
authors.affiliation: Divisão de Farmacologia, Instituto Nacional de Câncer, São Paulo, Brazil.
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Vargens
authors.forename: Ronaldo R S
authors.initials: RR
authors.lastname: Neves
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bulzico
authors.forename: Elida B
authors.initials: EB
authors.lastname: Ojopi
authors.forename: Ricardo M R
authors.initials: RM
authors.lastname: Meirelles
authors.forename: Cencita N
authors.initials: CN
authors.lastname: Pessoa
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Prado
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Gonçalves
authors.forename: Vera L G
authors.initials: VL
authors.lastname: Leal
authors.forename: Guilherme
authors.initials: G
authors.lastname: Suarez-Kurtz
mesh_terms: D000483:Alleles; D002454:Cell Differentiation; D004273:DNA, Neoplasm / Q000235:genetics; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D013972:Thyrotropin; D013974:Thyroxine / Q000627:therapeutic use*; D000099148:UGT1A1 Enzyme
chemical_list: D004273:DNA, Neoplasm; D014453:Glucuronosyltransferase; D013972:Thyrotropin; D013974:Thyroxine; D000099148:UGT1A1 Enzyme