Association of the UGT1A1-53(TA)n polymorphism with L-thyroxine doses required for thyrotropin suppression in patients with differentiated thyroid cancer

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 transferas...

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Published inPharmacogenetics and genomics Vol. 21; no. 6; p. 341
Main Authors Vargens, Daniela D, Neves, Ronaldo R S, Bulzico, Daniel A, Ojopi, Elida B, Meirelles, Ricardo M R, Pessoa, Cencita N, Prado, Carolina M, Gonçalves, Pedro A, Leal, Vera L G, Suarez-Kurtz, Guilherme
Format Journal Article
LanguageEnglish
Published United States 01.06.2011
Subjects
Alleles
Cell Differentiation
DNA, Neoplasm - genetics
Genotype
Glucuronosyltransferase - genetics
Humans
Polymerase Chain Reaction
Polymorphism, Genetic - genetics
Thyroid Neoplasms - drug therapy
Thyroid Neoplasms - genetics
Thyroid Neoplasms - pathology
Thyrotropin
Thyroxine - therapeutic use
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Summary: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.
ISSN:1744-6880
DOI:10.1097/FPC.0b013e3283448d19