Cyp-450 基因的多态性与疟疾：基因型和表型与治疗失败的关系

IF 3 4区医学 Q2 INFECTIOUS DISEASES

Brazilian Journal of Infectious Diseases Pub Date : 2024-11-01 DOI:10.1016/j.bjid.2024.104400

Marcelo Cerilo-Filho , Maria Naely Gomes Almeida , Marrara Pereira Sampaio , Dulce Jorge Viagem , Rayanne Iane Correa , Nathália Faria Reis , Andréa Regina de Souza Baptista , Ricardo Luiz Dantas Machado

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引用次数: 0

摘要

导言疟疾患者治疗失败的原因有多种，而负责氯喹和伯氨喹约 90% 代谢的细胞色素 P450（CYP450）家族酶的多态性可导致抗疟药物的低代谢、中等代谢或快速代谢。方法研究问题采用 PICO 格式（人群 = 间日疟原虫感染者；干预 = 无间日疟；比较 = CPY450 基因的多态性；结果 = 抗疟药物的生物代谢受 CYP450 基因多态性的影响）。对数据库（Medline、Pubmed、Google scholar、Science direct 和 Scopus）的调查是通过布尔运算符（AND/OR）对描述符（DECs/Mesh）进行分组的。结果在检索到的 187,935 篇文章中，仅有 12 篇被选中用于本次综述，共计 2050 人。大多数文章（75%）报告了恶性疟原虫感染者的 CYP2A6、CYP2D6、CYP2B6、CYP3A4 和 CYP3A5 基因多态性与药物代谢干扰之间的相互作用。至于间日疟原虫（25%），CYP2D6 基因中的 SNP 是导致治疗失败的最常见原因。在生物代谢表型方面，65%为正常代谢者，25%为低代谢者，5%为快速代谢者，5%为无效代谢者。结论：在疟疾流行地区的人群中制定旨在分析遗传生物标志物及其各自表型的措施非常重要，以防止间日疟复发和两种疟原虫的治疗失败；这对制定疟疾预防和控制措施非常重要：无利益冲突。

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POLYMORPHISMS IN THE CYP-450 GENE AND MALARIA: A GENOTYPIC AND PHENOTYPIC RELATIONSHIP WITH THERAPEUTIC FAILURE

Introduction

Therapeutic failure in patients with malaria can occur due to various factors and polymorphisms in enzymes of the Cytochrome P450 (CYP450) family, responsible for around 90% of the metabolization of chloroquine and primaquine, can generate individuals who are low, intermediate or fast metabolizers of antimalarial drugs.

Objective

We evaluated the relationship between these polymorphisms and the biometalization of antimalarial drugs worldwide through a systematic review using the PRISMA statement.

Methodology

The research question was structured in the PICO format (Population = people infected with Plasmodium vivax; Intervention = people without vivax malaria; Comparison = polymorphisms in the CPY450 gene; Outcome = biometabolization of antimalarial drugs is influenced by polymorphisms in the CYP450 gene). The investigation in the databases (Medline through Pubmed, Google scholar, Science direct and Scopus) was carried out by grouping descriptors (DECs/Mesh) with Boolean operators (AND/OR). Duplicate articles were excluded, as well as those with in vitro research, which did not meet the objective of the study and which, when applying the Joanna Briggs Institute questionnaire, had ≤ 50% "yes" answers.

Results

Of the 187,935 articles retrieved, only 12 were selected for this review, adding up to 2050 individuals. The majority (75%) of the articles reported an interaction between polymorphisms in the CYP2A6, CYP2D6, CYP2B6, CYP3A4 and CYP3A5 genes in individuals infected with Plasmodium falciparum and interference in drug metabolization. As for Plasmodium vivax (25%), the SNP in the CYP2D6 gene was the most frequently reported cause of therapeutic failure. As for the phenotype regarding biometabolization, 65% were normal, 25% low, 5% fast and 5% null metabolizers. Conclusions: It is important to develop measures aimed at profiling genetic biomarkers and their respective phenotypes in populations from endemic areas, in order to prevent relapses from P. vivax and treatment failure for both plasmodia; important for establishing malaria prevention and control measures.

Keywords

Molecular Epidemiology, Pharmacogenetics, Plasmodium, Public Health.

Conflicts of interest

There was no conflicts of interest.

Ethics and financing: Declarations of interest

None.

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来源期刊

Brazilian Journal of Infectious Diseases 医学-传染病学

CiteScore

5.50

自引率

0.00%

发文量

925

审稿时长

41 days

期刊介绍： The Brazilian Journal of Infectious Diseases is the official publication of the Brazilian Society of Infectious Diseases (SBI). It aims to publish relevant articles in the broadest sense on all aspects of microbiology, infectious diseases and immune response to infectious agents. The BJID is a bimonthly publication and one of the most influential journals in its field in Brazil and Latin America with a high impact factor, since its inception it has garnered a growing share of the publishing market.