哥伦比亚波哥大 CYP2C19 多态性的流行情况:等位基因*17 的首次报告。

Prevalence of CYP2C19 polymorphism in Bogotá, Colombia: The first report of allele *17.

机构信息

Departamento de Microbiología, Grupo de Enfermedades Infecciosas, Laboratorio de Bacteriología Especial, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.

Facultad de Medicina, Unidad de Gastroenterología, Universidad Nacional de Colombia, Bogotá D.C., Colombia.

出版信息

PLoS One. 2021 Jan 27;16(1):e0245401. doi: 10.1371/journal.pone.0245401. eCollection 2021.

Abstract

INTRODUCTION

Proton pump inhibitors (PPIs) are a group of drugs that are essential for the treatment of acid-related disorders, such as gastroesophageal reflux (GERD), dyspepsia, gastric ulcers and Helicobacter pylori (H. pylori) infection. PPIs such as omeprazole, esomeprazole, pantoprazole and lansoprazole are metabolized by the CYP2C19 enzyme, which is encoded by a polymorphic gene. Four polymorphisms have an impact on the speed of PPI metabolism: CYP2C19*1/1 (extensive metabolizers), CYP2C192/2 (intermediate metabolizers), CYP2C193/3 (poor metabolizers) and CYP2C1917/*17 (ultrarapid metabolizers). Extensive and ultrarapid metabolizers inactivate PPIs quickly, which consequently causes low plasma concentrations of PPIs, while intermediate or poor metabolizers have higher plasma concentrations of PPIs and, therefore, PPIs have greater therapeutic efficacy in individuals with these polymorphisms.

OBJECTIVE

To determine the frequency of genetic polymorphisms of the CPY2C19 enzyme in Bogotá, Colombia.

METHODS

This observational study was conducted in Bogotá between 2012 and 2015 and was part of a clinical trial (ID: NCT03650543). It included 239 subjects with dyspepsia, H. pylori infection, or GERD symptoms. CYP2C19 genotyping was performed on gastric biopsy samples. Polymorphisms *1, *2, and *3 were analyzed by real-time PCR (Roche®), and PCR-RFLP was used to determine the presence of polymorphism *17.

RESULTS

The distribution of different types of PPI metabolizers was as follows: extensive (70.7%), ultrarapid (12.9%), intermediate (8.8%) and poor (0.8%).

CONCLUSION

The population studied consisted mainly of extensive and ultrarapid PPI metabolizers. These findings show that it is necessary to increase PPI doses in this group of subjects or to use PPIs that are not metabolized by CYP2C19 (rabeprazole). This is the first Colombian work to identify ultrarapid metabolizers.

摘要

简介

质子泵抑制剂(PPIs)是一组用于治疗酸相关疾病的药物,如胃食管反流病(GERD)、消化不良、胃溃疡和幽门螺杆菌(H. pylori)感染。奥美拉唑、埃索美拉唑、泮托拉唑和兰索拉唑等 PPI 由 CYP2C19 酶代谢,该酶由多态性基因编码。四种多态性影响 PPI 代谢速度:CYP2C19*1/1(广泛代谢者)、CYP2C192/2(中间代谢者)、CYP2C193/3(弱代谢者)和 CYP2C1917/*17(超快代谢者)。广泛和超快代谢者快速灭活 PPI,导致 PPI 血浆浓度降低,而中间或弱代谢者 PPI 血浆浓度较高,因此这些多态性个体的 PPI 治疗效果更好。

目的

确定哥伦比亚波哥大 CYP2C19 酶的遗传多态性频率。

方法

这是一项在 2012 年至 2015 年间在波哥大进行的观察性研究,是一项临床试验的一部分(ID:NCT03650543)。它包括 239 名患有消化不良、H. pylori 感染或 GERD 症状的患者。对胃活检样本进行 CYP2C19 基因分型。通过实时 PCR(罗氏®)分析多态性1、2 和3,PCR-RFLP 用于确定多态性17 的存在。

结果

不同类型 PPI 代谢者的分布如下:广泛代谢者(70.7%)、超快代谢者(12.9%)、中间代谢者(8.8%)和弱代谢者(0.8%)。

结论

研究人群主要由广泛和超快 PPI 代谢者组成。这些发现表明,有必要增加该组受试者的 PPI 剂量,或使用不由 CYP2C19 代谢的 PPI(雷贝拉唑)。这是第一项确定超快代谢者的哥伦比亚研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/448a/7840015/5977facebe46/pone.0245401.g001.jpg

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