基于生物芯片的综合药物遗传学检测方法。

Biochip-based approach for comprehensive pharmacogenetic testing.

作者信息

Ikonnikova Anna Yu, Filippova Marina A, Surzhikov Sergey A, Pozhitnova Victoria O, Kazakov Ruslan E, Lisitsa Tatiana S, Belkov Sergey A, Nasedkina Tatiana V

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

Federal State Budgetary Institution "Scientific Centre for Expert Evaluation of Medicinal Products" of the Ministry of Health of the Russian Federation, Moscow, Russia.

出版信息

Drug Metab Pers Ther. 2020 Dec 14. doi: 10.1515/dmpt-2020-0155.

DOI:10.1515/dmpt-2020-0155

PMID:33780199

Abstract

OBJECTIVES

Individual sensitivity to many widely used drugs is significantly associated with genetic factors. The purpose of our work was to develop an instrument for simultaneous determination of the most clinically relevant pharmacogenetic markers to allow personalized treatment, mainly in patients with cardiovascular diseases.

METHODS

Multiplex one-step polymerase chain reaction (PCR) followed by hybridization on a low-density biochip was applied to interrogate 15 polymorphisms in the following eight genes: -1639 G>A 1297 G>A 2374 C>G *2,*3 (430 C>T, 1075 A>C) (2549delA, 1846 G>A, 1707delT, 2615_2617delAAG, 2988 G>A), (681 G>A, 636 G>A, -806 C>T) (3435 C>T).

RESULTS

Two hundred nineteen patients with cardiovascular diseases (CVD) and 48 female patients with estrogen receptor (ER)-positive breast cancer (BC) were genotyped. Of the 219 CVD patients, 203 (92.7%) carried one or more actionable at-risk genotypes based on and genotypes. Among them, 67 patients (30.6%) carried one, 58 patients (26.5%) carried two, 51 patients (23.3%) carried three, 26 patients (11.9%) carried four, and one patient (0.4%) carried five risk actionable genotypes. In the ER-positive BC group 12 patients (25%) were intermediate or poor metabolizers.

CONCLUSIONS

The developed biochip is applicable for rapid and robust genotyping of patients who were taking a wide spectrum of medications to optimize drugs and dosage and avoid adverse drug reactions in cardiology, oncology, psychiatry, rheumatology and gastroenterology.

摘要

目的

个体对许多广泛使用药物的敏感性与遗传因素显著相关。我们研究的目的是开发一种用于同时测定最具临床相关性的药物遗传学标志物的工具，以实现个性化治疗，主要针对心血管疾病患者。

方法

采用多重一步聚合酶链反应（PCR），随后在低密度生物芯片上进行杂交，以检测以下八个基因中的15个多态性： -1639 G>A 1297 G>A 2374 C>G *2,*3（430 C>T，1075 A>C）（2549delA，1846 G>A，1707delT，2615_2617delAAG，2988 G>A），（681 G>A，636 G>A， -806 C>T）（3435 C>T）。

结果

对219例心血管疾病（CVD）患者和48例雌激素受体（ER）阳性乳腺癌（BC）女性患者进行基因分型。在219例CVD患者中，根据和基因型，203例（92.7%）携带一种或多种可采取行动的风险基因型。其中，67例患者（30.6%）携带一种，58例患者（26.5%）携带两种，51例患者（23.3%）携带三种，26例患者（11.9%）携带四种，1例患者（0.4%）携带五种风险可采取行动的基因型。在ER阳性BC组中，12例患者（25%）为中间或慢代谢者。