Background: AT1R (Angiotensin II type 1 receptor) is the main component of RAS (renin-angiotensin system)
system which activates when ANG II (angiotensin II) binds to it. AT1R helps in maintaining osmotic homeostasis and
blood pressure regulation. A huge number of polymorphism is associated with AT1R and few of them were studied and
found to be associated with the diseases and drug efficacy. Although it is very important receptor but most of the
polymorphisms (SNPs) were not studied for their implications in diseases. Huge number of polymorphisms is reported in
the databases for AT1R which provide an avenue to explore these polymorphisms for their implications in protein
structure, function and drug efficacy.
Methods: In the current study all the SNPs (10234) reported in NCBI were analyzed and SNPs which were important in
protein structure and drug interactions were identified. Structures of these polymorphic forms were modeled and in silico
drug interaction studies were carried out.
Results: Result of the interaction studies with polymorphism was in correlation with the reported case. Two SNP mutated
structures of AT1R i.e. rs780860717 (G288T), rs868647200 (A182C) shows considerably less binding affinities in case of
all angiotensin receptor blockers (ARBs). As a result these polymorphisms may show less efficacy toward these ARBs.
The other mutated structures rs12721226 (A163G), rs749234826 (A292G), rs775810028 (A87G) shows increased binding
affinities in case of Eprosartan and most of the mutated structures shows increased binding affinity toward Telmisartan
than the wild type AT1R. Similarly, these polymorphisms may show increased efficacy in case of these two ARBs.
Conclusion: The outcome of the study will help in designing better drugs in near future with broader spectrum.
Furthermore in vitro and in vivo studies can be designed according to current results.