Öztaş Ezgi, Parejo Garcia-Saavedra Alejandro, Yanar Fatih, Özçinar Beyza, Aksakal Nihat, Purisa Sevim, Özhan Gül
Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, 34116 Beyazit, Istanbul, Turkey.
Istanbul University, Faculty of Medicine, Department of General Surgery, 34093 Fatih, Istanbul, Turkey.
Saudi Pharm J. 2018 Feb;26(2):274-278. doi: 10.1016/j.jsps.2017.11.012. Epub 2017 Nov 27.
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 (, ), 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).
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.
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, TTT and CGC 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 polymorphisms and L-T4 doses.
Because of conflicted previous reports about the genetic contribution of polymorphisms to drug disposition, further studies with large numbers of participants are required to clarify this influence.
P-糖蛋白（P-gp）参与多种药物的处置过程；因此，P-gp编码基因中的单核苷酸多态性（SNP）可能会影响其活性。众所周知，个性化医疗而非经验性治疗是提高患者治疗反应的重要临床方法。事实上，有必要评估P-gp编码的多药耐药基因（ ）的SNP与这些药物剂量需求之间的关联。在本研究中，我们评估了左甲状腺素（L-T4）剂量与三个常见SNP（C1236T、G2677T/A和C3435T）之间的关联。
使用实时PCR平台对从90例甲状腺切除术后甲状腺功能减退患者的静脉血中分离的DNA样本进行基因分型。甲状腺激素水平在伊斯坦布尔大学医学院的常规生物化学实验室进行检测。
在基因型分析中，C1236T的次要等位基因频率为0.48，G2677T/A为0.51，C3435T为0.51。在基于单倍型的分析中，观察到TTT和CGC为主要单倍型（分别为50.2%和32.6%），与先前的研究一致。发现所有基因型和单倍型中，为达到生理甲状腺激素水平而给予的L-T4剂量相似，这表明多态性与L-T4剂量之间无显著关联。
由于先前关于多态性对药物处置的遗传贡献的报道存在矛盾，需要更多参与者进行进一步研究以阐明这种影响。
