Pharmacogenetic analysis of captopril effects on blood pressure: possible role of the Ednrb (endothelin receptor type B) candidate gene.
The objective of the current study was to search for genetic determinants associated with antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitor captopril. Linkage and correlation analyses of captopril-induced effects on blood pressure (BP) with renal transcriptome were performed in the BXH/HXB recombinant inbred (RI) strains derived from spontaneously hypertensive rat (SHR) and Brown Norway (BN-Lx) progenitors. Variability of blood pressure lowering effects of captopril among RI strains was continuous suggesting a polygenic mode of inheritance. Linkage analysis of captopril-induced BP effects revealed a significant quantitative trait locus (QTL) on chromosome 15. This QTL colocalized with cis regulated expression QTL (eQTL) for the Ednrb (endothelin receptor type B) gene in the kidney (SHR allele was associated with increased renal expression) and renal expression of Ednrb correlated with captopril-induced BP effects. These results suggest that blood pressure lowering effects of ACE inhibitor captopril may be modulated by the variants at the Ednrb locus.
Institute of Physiology Academy of Sciences of the Czech Republic, Prague, Czech Republic. pravenec@biomed.cas.cz.
J
J
Zicha
Z
Z
Dobešová
V
V
Zídek
J
J
Silhavý
M
M
Simáková
P
P
Mlejnek
I
I
Vaněčková
J
J
Kuneš
M
M
Pravenec
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology*; D056726:Genetic Association Studies / Q000379:methods*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*
D000959:Antihypertensive Agents; C000588596:EDNRB protein, human; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D002216:Captopril