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.