RESUMO
AIM: To evaluate the impact of genetic polymorphisms in uridine 5'-glucuronosylytansferases UGT1A1 and UGT1A3 and iodothyronine-deiodinases types 1 and 2 on levothyroxine (T4 ; 3,5,3',5'-triiodo-L-thyronine) dose requirement for suppression of thyrotropin (TSH) secretion in patients with differentiated thyroid cancer (DTC). METHODS: Patients (n = 268) submitted to total thyroidectomy and ablation by (131) I, under T4 therapy for at least 6 months were recruited in three public institutions in Brazil. Multivariate regression modelling was applied to assess the association of T4 dosing with polymorphisms in UGT1A1 (rs8175347), UGT1A3 (rs3806596 and rs1983023), DIO1 (rs11206244 and rs2235544) and DIO2 (rs225014 and rs12885300), demographic and clinical variables. RESULTS: A regression model including UGT1A haplotypes, age, gender, body weight and serum TSH concentration accounted for 39% of the inter-individual variation in the T4 dosage. The association of T4 dose with UGT1A haplotype is attributed to reduced UGT1A1 expression and T4 glucuronidation in liver of carriers of low expression UGT1A1 rs8175347 alleles. The DIO1 and DIO2 genotypes had no influence of T4 dosage. CONCLUSION: UGT1A haplotypes associate with T4 dosage in DTC patients, but the effect accounts for only 2% of the total variability and recommendation of pre-emptive UGT1A genotyping is not warranted.
Assuntos
Adenocarcinoma Folicular/tratamento farmacológico , Carcinoma/tratamento farmacológico , Glucuronosiltransferase/genética , Iodeto Peroxidase/genética , Polimorfismo Genético , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina/antagonistas & inibidores , Tiroxina/administração & dosagem , Adenocarcinoma Folicular/sangue , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Adulto , Carcinoma/sangue , Carcinoma/genética , Carcinoma/patologia , Carcinoma Papilar , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Tireotropina/sangue , Tiroxina/uso terapêutico , Iodotironina Desiodinase Tipo IIRESUMO
In this paper we calculate the variation of the estimated vaccine efficacy (VE) due to the time-dependent force of infection resulting from the difference between the moment the Clinical Trial (CT) begins and the peak in the outbreak intensity. Using a simple mathematical model we tested the hypothesis that the time difference between the moment the CT begins and the peak in the outbreak intensity determines substantially different values for VE. We exemplify the method with the case of the VE efficacy estimation for one of the vaccines against the new coronavirus SARS-CoV-2.