Single nucleotide polymorphism (SNP) rs4291 of the angiotensin-converting enzyme (ACE) gene is associated with the response to losartan treatment in hypertensive patients

• Published in: Molecular biology reports Vol. 51; no. 1; p. 458
• Main Authors: da Cunha Agostini, Lívia, de Paula, Waléria, Melo, André Sacramento, Silva, Nayara Nascimento Toledo, Faria Lopes, Ana Cláudia, de Almeida Belo, Vanessa, Coura-Vital, Wendel, de Medeiros Teixeira, Luiz Fernando, Lima, Angélica Alves, da Silva, Glenda Nicioli
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-12-2024; Springer Nature B.V
• Subjects: ACE protein; Angiotensin; Angiotensins; Animal Anatomy; Animal Biochemistry; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Antihypertensives; Biomedical and Life Sciences; Blood pressure; Blood Pressure - genetics; Case-Control Studies; Enzymes; Gene polymorphism; Histology; Humans; Hydrochlorothiazide; Hydrochlorothiazide - pharmacology; Hydrochlorothiazide - therapeutic use; Hypertension; Hypertension - drug therapy; Hypertension - genetics; Life Sciences; Losartan - pharmacology; Losartan - therapeutic use; Morphology; Original Article; Patients; Peptidyl-dipeptidase A; Polymorphism, Single Nucleotide - genetics; Single-nucleotide polymorphism; Spectrophotometry; Hypertension; Pharmacogenetic; Hydrochlorothiazide; Angiotensin converting enzyme gene; Losartan
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-024-09437-1

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the
ACE
gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of
ACE
rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of
ACE
variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of
ACE
polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12–6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of
ACE
polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system.