Renin and CYP P450 gene variations significantly associated with essential hypertension: A prospective pharmacogenomics study

Abstract

Objective

This study aims to investigate the association between Renin-angiotensin aldosterone system (RAAS) and Cytochrome P450 gene polymorphisms in hypertension patients of the South Indian population using pharmacogenomics profile.

Methods

Hypertension cases (N = 147) and control subjects (n = 150) were collected from Tamil Nadu, India. A case-control association study was conducted to assess the involvement of RAAS gene polymorphisms (REN rs397514691, REN rs544315427, REN rs567667202) and CYP gene polymorphisms (CYP2D6 rs754164689, CYP2D6 rs1058172, CYP3A4 rs765598920) in essential hypertensive patients. Genotyping was performed using the PCR-RFLP method, and significant results were validated through RT-PCR analysis.

Results

The genotype and allele distribution of REN rs397514691 and rs544315427 variants significantly associated with hypertensive patients (Variant Allele Frequency (VAF) = 0.11; VAF = 0.27, respectively). CYP2D6 polymorphisms rs754164689 and rs1058172 variant alleles were significantly associated with female hypertensive patients, suggesting a potential risk allele for essential hypertension in the South Indian population. REN and CYP3A4 variants, highly connected in pharmacology action, were validated through RT-PCR amplification studies, providing new insights into their role in the development of hypertension. Association confirmation was achieved through multifactor dimensionality reduction analysis.

Conclusion

The genes associated with specific variants, particularly REN and CYP2D6, may serve as potential markers for the early diagnosis of hypertension and as new drug targets, particularly in the female population.