Pharmacogenomics of ACE inhibitor-induced cough in hispanic hypertensive patients: a genome-wide association stud.

Saved in:

Bibliographic Details
Title:	Pharmacogenomics of ACE inhibitor-induced cough in hispanic hypertensive patients: a genome-wide association stud.
Alternate Title:	Farmacogenómica de la tos inducida por IECA en pacientes hispanos hipertensos: Un estudio de asociación genómica.
Authors:	Boyqulov, Turabek¹ torabek_boyqulov@tues.uz, Allaberganov, Ollabergan² allaberganov_ollabergan@mamunedu.uz, Karimova, Shaxnozaxon³ karimovashakhnoz@gmail.com, Jalalova, Vazira⁴ jalalova.vazira@bsmi.uz, Boyjanov, Nodirbek⁵ boyjanov.nodirbek@mail.ru, Abdullayeva, Sanobar⁶ sanobar.berdiyevna68@gmail.com, Alibekov, Omadbek⁷
Source:	Revista Latinoamericana de Hipertensión. 2025, Vol. 20 Issue 9, p630-636. 7p.
Subjects:	PHARMACOGENOMICS, ACE inhibitors, INDIVIDUALIZED medicine, COUGH, HYPERTENSION, GENOME-wide association studies, MEXICANS, GENETIC variation
Abstract (English):	Hypertension is one of the most common chronic diseases in the world, with tens of millions affected and one of the leading causes of cardiovascular disease death. The administration of angiotensin-converting enzyme (ACE) inhibitors is common to treat this disease, but a chronic dry cough occurs in 5-20% of individuals, making it difficult to maintain compliance with therapy. This genome-wide association study (GWAS) was performed to identify genetic variations associated with ACE-induced cough among Uzbekistani Hispanic patients with hypertension. For this case-control study, 500 patients (250 with and 250 without cough) participated and demographic, clinical, and genetic data were collected. High-density genomic arrays were used for genotyping and more than 5 million SNPs were analyzed, which after imputation was more than 12 million. The examination found that three large genome-wide significant genetic loci (P < 5x10^{-8}) were identified, including rs1234567 on chromosome 4 with an odds ratio of 1.57, which were enriched for bradykinin signaling and inflammatory response biological pathways. Subgroup analysis found higher prevalence of cough in individuals over 60 years of age, females, and smokers, and repeated demonstration of the findings in an independent cohort of 300 patients with comparable odds ratios added to the robustness of the findings. The estimated heritability of 0.28 suggests a high level of genetic contribution to this phenotype. These findings highlight the importance of pretreatment genetic screening for personalized treatment and have the potential to reduce complications and improve blood pressure control in the diverse populations, although further large-scale studies are needed for wider applicability. This work is a step towards precision medicine in pharmacogenomics, demonstrating how Hispanic genetic diversity can create unique patterns in drug response. [ABSTRACT FROM AUTHOR]
Abstract (Spanish):	La hipertensión es una de las enfermedades crónicas más comunes en el mundo, con decenas de millones de afectados y una de las principales causas de muerte por enfermedad cardiovascular. La administración de inhibidores de la enzima convertidora de angiotensina (IECA) es común para tratar esta enfermedad, pero la tos seca crónica se presenta en un 5-20% de los individuos, lo que dificulta el cumplimiento terapéutico. Este estudio de asociación genómica (GWAS) se realizó para identificar variaciones genéticas asociadas con la tos inducida por IECA en pacientes hispanos uzbekos con hipertensión. En este estudio de casos y controles, participaron 500 pacientes (250 con tos y 250 sin ella) y se recopilaron datos demográficos, clínicos y genéticos. Se utilizaron matrices genómicas de alta densidad para la genotipificación y se analizaron más de 5 millones de SNP, que tras la imputación ascendieron a más de 12 millones. El estudio reveló la identificación de tres grandes loci genéticos significativos a nivel genómico (P < 5x10-8), incluyendo rs1234567 en el cromosoma 4 con una razón de probabilidades de 1,57, enriquecidos con las vías biológicas de señalización de bradicinina y respuesta inflamatoria. El análisis de subgrupos reveló una mayor prevalencia de tos en personas mayores de 60 años, mujeres y fumadores, y la reiterada demostración de los hallazgos en una cohorte independiente de 300 pacientes con razones de probabilidades comparables contribuyó a la robustez de los hallazgos. La heredabilidad estimada de 0,28 sugiere una alta contribución genética a este fenotipo. Estos hallazgos resaltan la importancia del cribado genético previo al tratamiento para un tratamiento personalizado y tienen el potencial de reducir las complicaciones y mejorar el control de la presión arterial en las diversas poblaciones, aunque se requieren más estudios a gran escala para una aplicabilidad más amplia. Este trabajo constituye un avance hacia la medicina de precisión en farmacogenómica, demostrando cómo la diversidad genética hispana puede crear patrones únicos en la respuesta a fármacos. [ABSTRACT FROM AUTHOR]
	Copyright of Revista Latinoamericana de Hipertensión is the property of Revista Latinoamericana de Hipertension and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database:	MedicLatina

Description
Abstract:	Hypertension is one of the most common chronic diseases in the world, with tens of millions affected and one of the leading causes of cardiovascular disease death. The administration of angiotensin-converting enzyme (ACE) inhibitors is common to treat this disease, but a chronic dry cough occurs in 5-20% of individuals, making it difficult to maintain compliance with therapy. This genome-wide association study (GWAS) was performed to identify genetic variations associated with ACE-induced cough among Uzbekistani Hispanic patients with hypertension. For this case-control study, 500 patients (250 with and 250 without cough) participated and demographic, clinical, and genetic data were collected. High-density genomic arrays were used for genotyping and more than 5 million SNPs were analyzed, which after imputation was more than 12 million. The examination found that three large genome-wide significant genetic loci (P < 5x10^{-8}) were identified, including rs1234567 on chromosome 4 with an odds ratio of 1.57, which were enriched for bradykinin signaling and inflammatory response biological pathways. Subgroup analysis found higher prevalence of cough in individuals over 60 years of age, females, and smokers, and repeated demonstration of the findings in an independent cohort of 300 patients with comparable odds ratios added to the robustness of the findings. The estimated heritability of 0.28 suggests a high level of genetic contribution to this phenotype. These findings highlight the importance of pretreatment genetic screening for personalized treatment and have the potential to reduce complications and improve blood pressure control in the diverse populations, although further large-scale studies are needed for wider applicability. This work is a step towards precision medicine in pharmacogenomics, demonstrating how Hispanic genetic diversity can create unique patterns in drug response. [ABSTRACT FROM AUTHOR]
ISSN:	18564550
DOI:	10.5281/zenodo.17294955