Sheikh Arooj Fatima, Munawar Nayla, Nawaz Rukhsana, Khan Hizbullah, Rafique Mehwish, Jahan Faryal, Ahmed Sagheer
Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan.
Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
Front Pharmacol. 2024 Sep 4;15:1441251. doi: 10.3389/fphar.2024.1441251. eCollection 2024.
Angiotensin-converting enzyme inhibitors (ACEIs) are prescribed for individuals with high cardiovascular (CV) risk; however, persistent cough limits the use of ACEIs in a large number of patients. The current study aimed to identify the genetic variants in the gene that might be associated with ACEI-related cough in a Pakistani hypertensive population.
A prospective cohort study was conducted at a tertiary care hospital in Pakistan. A total of 74 patients who had been treated with ACEIs were recruited through a convenient sampling method. The study was approved by the Institutional Review Board & Ethics Committee of the Shifa International Hospital, Islamabad. Patients provided 2 ml of blood for sequencing after signing informed consent. Partial gene sequencing of was carried out to find single nucleotide polymorphisms (SNPs) and haplotypes.
It was found, through a structured questionnaire, that thirty-eight (38) patients experienced cough within 2 weeks of ACEI administration and were considered as a case group (cough), and thirty-six (36) patients were considered as a control group (no cough). The incidence of cough was 51%. We found six different SNPs and 9 haplotypes in the partial gene sequences of Haplotype H4 was associated significantly with cough after adjusting for sex and smoking status. Other SNPs and haplotypes were not significantly associated with ACE-Is-induced cough.
These findings emphasize the significance of genetic variants, specifically H4, as a potential predictor of ACEI-induced cough. It could be included in clinical practice as a possible risk factor for ACEI-induced cough once confirmed in larger clinical trials with bigger sample sizes. The replication of these findings in larger and more diverse populations is likely to contribute to the therapeutic use of ACEIs by predicting ACEI-induced cough.
血管紧张素转换酶抑制剂（ACEI）被用于心血管（CV）风险较高的个体；然而，持续性咳嗽限制了其在大量患者中的使用。本研究旨在确定在巴基斯坦高血压人群中，该基因中可能与ACEI相关咳嗽有关的基因变异。
在巴基斯坦一家三级护理医院进行了一项前瞻性队列研究。通过方便抽样法招募了74例接受过ACEI治疗的患者。该研究获得了伊斯兰堡希法国际医院机构审查委员会和伦理委员会的批准。患者在签署知情同意书后提供2毫升血液用于测序。对该基因进行部分基因测序以寻找单核苷酸多态性（SNP）和单倍型。
通过结构化问卷发现，38例患者在服用ACEI后2周内出现咳嗽，被视为病例组（咳嗽），36例患者被视为对照组（无咳嗽）。咳嗽发生率为51%。我们在该基因的部分基因序列中发现了6种不同的SNP和9种单倍型。在调整性别和吸烟状况后，单倍型H4与咳嗽显著相关。其他SNP和单倍型与ACEI引起的咳嗽无显著关联。
这些发现强调了该基因变异，特别是H4，作为ACEI引起咳嗽的潜在预测指标的重要性。一旦在更大样本量的大型临床试验中得到证实，它可作为ACEI引起咳嗽的可能危险因素纳入临床实践。在更大、更多样化的人群中重复这些发现，可能有助于通过预测ACEI引起的咳嗽来指导ACEI的治疗应用。
