P-glycoprotein polymorphism and levothyroxine bioavailability in hypothyroid patients

Abstract

Objectives: P-glycoprotein (P-gp) contributes to the disposition of a wide variety of drugs; therefore, single nucleotide polymorphisms (SNPs) in the P-gp coding gene might affect its activity. It is well known that personalized medicine, instead of empirical treatment, is a clinically important approach for enhancing responses among patients. Indeed, there is a need to evaluate the association between SNPs of P-gp encoded multidrug resistance genes (MDR1, ABCB1), and the dosage requirements of these drugs. In the present study, we evaluated the association between the dosage of Levothyroxine (L-T4) and three common SNPs (C1236T, G2677T/A and C3435T). Methods: Genotyping was done using a real-time PCR platform with DNA samples isolated from the venous blood of ninety post thyroidectomy hypothyroid patients. Thyroid hormone levels were measured as routine biochemistry laboratories in the Medical School of Istanbul University. Results: In the genotype analysis, the minor allele frequencies were 0.48 for C1236T, 0.51 for G2677T/A, and 0.51 for C3435T. In the haplotype-based analysis, T1236T2677T3435 and C1236G2677C3435 were observed as major haplotypes (50.2 and 32.6%, respectively), in agreement with previous studies. The administered dose of L-T4 to achieve physiological thyroid hormone levels was found to be similar in all genotypes and haplotypes, indicating that there is no significant association between MDR1 polymorphisms and L-T4 doses. Conclusion: Because of conflicted previous reports about the genetic contribution of MDR1 polymorphisms to drug disposition, further studies with large numbers of participants are required to clarify this influence.

Keywords

• P-glycoprotein
• MDR1 polymorphisms
• Levothyroxine
• Hypothyroidism