In Silico Analysis of Human AGTR1 Gene and Precision Medicine Among Hypertensive Population
Renin-angiotensin-aldosterone system (RAAS) is the most important regulator of blood pressure to maintain homeostasis and vascular tone. The effect is mediated by four primary genes: angiotensinogen (AGT), renin (REN), angiotensin-I-converting enzyme (ACE), and angiotensin II receptor, subtype I (AGTRI). To study the role of AGTR1 gene polymorphisms influencing pharmacogenetics of hypertension was carried out by in silico analysis. This work helps in predicting functional biological variables, viz., genetic polymorphisms, which act as markers to predict individual’s response to drugs. Knowledge of pharmacogenetics helps in optimization of therapeutic strategies, based on the individualization of pharmacological treatment. This study is an attempt to predict possible structure-activity relationship effect of nsSNPs. These were analyzed using SIFT and PolyPhen-2. It is hypothesized that these variations have the potential to result in differential drug response and were further investigated by subsequent empirical approach as no population data is available for many of these SNPs. AGTR1 nsSNP rs12721226 (A163T) resulting in change from alanine to threonine at position 163 in AGTRI protein was investigated. The analysis included 300 clinically diagnosed hypertensive patients with/without associated metabolic disorders and 100 normal healthy subjects with their informed consent. Study has been approved by institutional clinical ethical committee vide No. ICEC/4/2011.
This work was supported by grant from the DBT-Punjabi University Interdisciplinary Life Science Programme for advanced research and education (DBT-IPLS Project) No. BT/PR-4548/INF/22/146/2012
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