In-silico analysis reveals druggable single nucleotide polymorphisms in angiotensin 1 converting enzyme involved in the onset of blood pressure.

Udosen, Brenda; Soremekun, Opeyemi; Ekenna, Chinwe; Idowu Omotuyi, Olaposi; Chikowore, Tinashe; Nashiru, Oyekanmi; Fatumo, Segun; (2021) In-silico analysis reveals druggable single nucleotide polymorphisms in angiotensin 1 converting enzyme involved in the onset of blood pressure. BMC research notes, 14 (1). 457-. ISSN 1756-0500 DOI: https://doi.org/10.1186/s13104-021-05879-z

Abstract

OBJECTIVE: The Angiotensin 1 converting enzyme (ACE1) gene plays a critical role in regulating blood pressure and thus, it has become a major therapeutic target of antihypertensives. Single nucleotide polymorphisms (SNPs) occurring within a gene most especially at the functional segment of the genes alter the structure-function relationship of that gene. RESULTS: Our study revealed that five nsSNPs of the ACE1 gene were found to be potentially deleterious and damaging and they include rs2229839, rs14507892, rs12709442, and rs4977 at point mutations P351R, R953Q, I1018T, F1051V, and T1187M. The protein stability predictive tools revealed that all the nsSNPs decreased stability of the protein and the Consurf server which estimates the evolutionary conservation profile of a protein showed that three mutants were in the highly conserved region. In conclusion, this study predicted potential druggable deleterious mutants that can be further explored to understand the pathological basis of cardiovascular disease.