Human pharmacogenomic variation of antihypertensive drugs: from population genetics to personalized medicine.
OBJECTIVE
To investigate the human pharmacogenetic variation related to antihypertensive drugs, providing a survey of functional interpopulation differences in hypertension pharmacogenes.


METHODS
The study was divided into two stages. In the first stage, we analyzed 1249 variants located in 57 hypertension pharmacogenes. This first-stage analysis confirmed that geographic origin strongly affects hypertension pharmacogenomic variation and that 31 pharmacogenes are geographically differentiated. In the second stage, we focused our attention on the ethnic-differentiated pharmacogenes, investigating 55,521 genetic variants. In silico analyses were performed to predict the effect of genetic variation.


RESULTS
Our analyses indicated functional interpopulation differences, suggesting insight into the mechanisms of antihypertensive drug response. Moreover, our data suggested that rare variants mainly determine the functionality of genes related to antihypertensive drugs.


CONCLUSIONS
Our study provided important knowledge about the genetics of the antihypertensive drug response, suggesting that next-generation sequencing technologies may develop reliable pharmacogenetic tests for antihypertensive drugs.
Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica 1, Rome, Italy.
Renato
R
Polimanti
Andrea
A
Iorio
Sara
S
Piacentini
Dario
D
Manfellotto
Maria
M
Fuciarelli
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D003198:Computer Simulation; D005828:Genetics, Population; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine
D000959:Antihypertensive Agents