Role of renin-angiotensin-aldosterone system gene polymorphisms in the development of diastolic dysfunction in female patients with hypertension

BACKGROUND: Cardiovascular diseases, including hypertension, cause approximately 17 million deaths annually, with 9.4 million directly attributable to hypertension, which affects nearly 40% of the adult population. Genetic polymorphisms in the renin-angiotensin-aldosterone system play a significant role in the development of hypertension and in response to therapy. Investigating candidate gene polymorphisms involved in renin-angiotensin-aldosterone system pathways may help optimize the selection of antihypertensive therapy at early stages of treatment.

AIM: To assess the frequency of single-nucleotide polymorphisms in renin-angiotensin-aldosterone system genes and their contribution to the development of diastolic dysfunction.

MATERIALS AND METHODS: A cross-sectional study was conducted in 87 postmenopausal women aged 67 years (interquartile range, 65–70 years). Single-nucleotide polymorphisms in the ADD1, AGT, AGTR1, AGTR2, CYP11B2, GNB3, NOS3 genes were analyzed using real-time polymerase chain reaction. Renin-angiotensin-aldosterone system-related gene polymorphisms were evaluated in patients with and without diastolic dysfunction, as assessed by transthoracic echocardiography.

RESULTS: No significant differences in the main clinical characteristics or the structure of antihypertensive therapy were observed between the groups with and without diastolic dysfunction (p >0.05). The current study did not reveal statistically significant differences in the distribution of polymorphic genotypes (p >0.05) The T allele of the CYP11B2 344 C/T polymorphism was significantly more frequent in patients with diastolic dysfunction. A two-locus model including AGT and CYP11B2 gene polymorphisms demonstrated a sensitivity of 66.1% and a specificity of 67.7%. The most effective three-locus model included polymorphisms in AGTR2, CYP11B2, and NOS3, yielding a sensitivity of 80.4% and a specificity of 71.0%.

CONCLUSION: Multilocus analysis and a predictive model based on a combination of gene polymorphisms may support the assessment of risk for developing diastolic dysfunction in patients with hypertension. Identifying the contribution of genetic factors to the development of cardiovascular diseases and understanding their clinical relevance may facilitate the personalization of therapy.