Department of Clinical Pharmacology, KEM Hospital, Parel, Mumbai, Maharashtra, India.
Indian J Pharmacol. 2022 Mar-Apr;54(2):97-101. doi: 10.4103/ijp.ijp_279_21.
CYP3A5 enzymes belong to the phase I Group of drug-metabolizing enzymes, which are involved in the metabolism of 50% of the drugs. Participants with CYP3A5 genotype: CYP3A5 *1/*1 are fast metabolizers of drugs and hence will require higher dosing. Whereas those with CYP3A5 * 3/*3 are poor metabolizers of drugs and will require a lower dose to achieve target drug concentration in the blood and those with CYP3A5 * 1/*3 have intermediate drug metabolizing activity. Pharmacogenetic evaluation may improve disease outcomes by maximizing the efficacy and minimizing the toxicity of drugs in patients.
This is a single-center cross-sectional study conducted in the year 2018-2019 to study the population prevalence of genetic polymorphisms of CYP3A5 in healthy participants from western India. Eligible participants willing to give written, informed consent were enrolled in the study. Subsequently, 2 ml venous blood was collected the deoxyribonucleic acid was extracted and then stored at ‒20°C. Genotyping was done by a polymerase chain reaction and restriction fragment length polymorphism.
A total of 400 participants with a median age of 22 years (range: 18-58 years) were included. Among them, the genotype prevalence for CYP3A5 * 1/*1 was 17% (n = 67/400); CYP3A5 * 1/*3 was 37% (n = 149/400) and that of CYP3A5 * 3/3 was 46% (184/400). Out of the total 400 healthy participants analyzed, the allele frequency for CYP3A5 * 1 was 35% (142/400) and that of CYP3A53 was 65% (259/400).
The genotype prevalence for CYP3A5 * 3*3 (46%) and the allele frequency for CYP3A5 * 3 (65%) respectively were the highest among the western Indian population.
CYP3A5 酶属于 I 相药物代谢酶组，参与代谢 50%的药物。具有 CYP3A5 基因型的参与者：CYP3A5*1/1 是药物的快速代谢者，因此需要更高的剂量。而 CYP3A53/3 是药物的不良代谢者，需要较低的剂量才能达到血液中目标药物浓度，CYP3A51/*3 具有中等药物代谢活性。药物遗传学评估可以通过最大限度地提高药物在患者中的疗效和最小化毒性来改善疾病结局。
这是一项 2018-2019 年在印度西部进行的单中心横断面研究，旨在研究健康参与者中 CYP3A5 遗传多态性的人群流行率。愿意书面知情同意的合格参与者被纳入研究。随后采集 2ml 静脉血，提取脱氧核糖核酸，然后储存在-20°C。通过聚合酶链反应和限制性片段长度多态性进行基因分型。
共纳入 400 名中位年龄为 22 岁（范围：18-58 岁）的参与者。其中，CYP3A51/1 的基因型流行率为 17%（n=67/400）；CYP3A51/3 为 37%（n=149/400），CYP3A53/3 为 46%（184/400）。在分析的 400 名健康参与者中，CYP3A51 的等位基因频率为 35%（142/400），CYP3A53 的等位基因频率为 65%（259/400）。
CYP3A533（46%）的基因型流行率和 CYP3A5*3（65%）的等位基因频率分别是印度西部人群中最高的。
