Gene Polymorphism of Angiotensin II Type 1 and Type 2 Receptors
Tomohiro Katsuya and Ryuichi Morishita
Affiliation: 2-17-21 Nanamatsu-cho, Amagasaki, Hyogo 660-0052, Japan.
Keywords: Renin angiotensin system (RAS), single nucleotide polymorphisms (SNPs), genetics, cardiovascular disease, genome wide association
study (GWAS), hypertension, left ventricular hypertrophy, angiotensin II receptor blocker (ARB).
Renin-angiotensin system (RAS) plays a key role in pathogenesis of cardiovascular disease and in the responsiveness for various
types of medications. A large number of genetic investigations have been carried out to examine the association between gene variants
of RAS and predisposition to cardiovascular diseases, such as hypertension, coronary artery disease and stroke. Even though the major
results were obtained from genetic association studies of angiotensinogen or angiotensin converting enzyme, unique findings were
also elucidated from investigations concerning single nucleotide polymorphisms (SNPs) of 2 types of angioteinsin II receptor genes denoted
as AGTR1 and AGTR2. Both genes have many SNPs in the coding and its flanking regions but most of the studies used A1166C
polymorphism of AGTR1 and G1675A polymorphism of AGTR2. In the subjects with C1166 allele of AGTR1, several investigations reported
increased risk for coronary artery disease, ischemic stroke, heart failure and end-stage renal disease but not for hypertension. Interestingly,
a few papers pointed out the possibility that A1166C modulates the efficacy of RAS inhibitors. In the genetic analysis of
AGTR2, G1675 allele carriers had increased risk for left ventricular hypertrophy, renal insufficiency and modulated hemodynamic response
to RAS inhibitors. In this review, we summarized previous investigations concerning the genetic aspects of AGTR1 and AGTR2 to
consider the clinical utility of SNPs of these receptors.
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