高血压患者中依那普利所致干咳继发发展的药物遗传学预测因素。

Pharmacogenetic predictors of development of secondary to enalapril dry cough in hypertensive patients.

作者信息

Sychev Ivan V, Denisenko Natalia P, Kachanova Anastasiya A, Lapshtaeva Anna V, Goncharova Ludmila N, Mirzaev Karin B, Sychev Dmitry A

机构信息

Department of Faculty Therapy with Courses of Physiotherapy, Physical Therapy, Ogarev Mordovia State University, Saransk, Russian Federation.

68, Bolshevitskaya Street, Saransk, Republic of Mordovia, 430005, Russia.

出版信息

Drug Metab Pers Ther. 2023 May 19;38(3):247-254. doi: 10.1515/dmpt-2023-0008. eCollection 2023 Sep 1.

DOI:10.1515/dmpt-2023-0008

PMID:37201212

Abstract

OBJECTIVES

Development of the secondary to ACEI cough leads to discontinuation of the drugs of this group. Assessing the safety of the ACEIs with further development of customized approaches for their administration is a major scientific and practical problem. The objective of this study was to assess the association of the genetic markers with the development of the adverse drug reaction in the form of secondary to enalapril dry cough in the patients with essential arterial hypertension.

METHODS

Study involved 113 patients with the secondary to enalapril cough and 104 patients without development of the secondary to enalapril adverse drug reaction.

RESULTS

The patients carriers of the genotype AA rs2306283 of gene SLCO1B1 had 2-fold higher odds of developing the dry cough than those with the genotypes AG and GG (ОR=2.01, 95%CI=1.10-3.66, р=0.023). Similarly, the patients heterozygous for rs8176746 of gene АВО had 2.3-fold higher odds of developing the ADR in the form of dry cough than the carriers of the genotypes GG and TT (ОR=2.30, 95%CI=1.24-4.29, р=0.008).

CONCLUSIONS

Statistically significant association between the development of the ADR in the form of secondary to enalapril dry cough and polymorphisms rs2306283 of gene SLCO1B1 and rs8176746 of gene ABO was revealed.

摘要

目的

血管紧张素转换酶抑制剂（ACEI）引发的咳嗽会导致该类药物停用。随着ACEI给药定制方法的进一步发展，评估其安全性是一个重大的科学和实际问题。本研究的目的是评估基因标记与原发性高血压患者中依那普利引发的干咳形式的药物不良反应发生之间的关联。

方法

研究纳入了113例出现依那普利引发咳嗽的患者和104例未出现依那普利药物不良反应的患者。

结果

基因SLCO1B1的rs2306283基因型为AA的患者发生干咳的几率比基因型为AG和GG的患者高2倍（比值比[OR]=2.01，95%置信区间[CI]=1.10 - 3.66，p = 0.023）。同样，基因ABO的rs8176746杂合子患者发生干咳形式药物不良反应的几率比基因型为GG和TT的携带者高2.3倍（OR = 2.30，95%CI = 1.24 - 4.29，p = 0.008）。