CAROLINA MARTINS DO PRADO
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
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- Association of the UGT1A1-53(TA)(n) polymorphism with L-thyroxine doses required for thyrotropin suppression in patients with differentiated thyroid cancer(2011) VARGENS, Daniela D.; NEVES, Ronaldo R. S.; BULZICO, Daniel A.; OJOPI, Elida B.; MEIRELLES, Ricardo M. R.; PESSOA, Cencita N.; PRADO, Carolina M.; GONCALVES, Pedro A.; LEAL, Vera L. G.; SUAREZ-KURTZ, GuilhermeThere is a considerable interindividual variation in L-thyroxine [ 3,5,3',5'-tetraiodo-l-thyronine (T-4)] dose required for thyrotropin (thyroid-stimulating hormone) suppression in patients with differentiated thyroid cancer. To investigate whether uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)-mediated T-4 glucuronidation in liver affects T-4 dose, we genotyped 101 patients for the common UGT1A1-53(TA)(n) polymorphism and compared T-4 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 T-4 dose with increasing number of copies of (TA)(7) and (TA)(8) (P = 0.037) and significant difference in T-4 dose across the UGT1A1-53(TA)(n) genotypes (P = 0.048) were observed, despite considerable overlap of T-4 doses among different genotypes. These results are consistent with reduced T-4 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 T-4-dose requirement for thyroid-stimulating hormone suppression in a natural clinical setting. Pharmacogenetics and Genomics 21: 341-343 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2011, 21: 341-343