Renin gene polymorphism: its relationship to hypertension, renin levels and vascular responses

Abstract

The renin gene has been previously reported to be associated with essential hypertension in a variety of ethnic groups. However, no studies have systematically evaluated the relationship between single nucleotide polymorphisms (SNPs) representing coverage of the entire renin gene and hypertension risk. To evaluate the association between renin gene variation and hypertension we investigated data on HyperPath cohort with 570 hypertensive and 222 normotensive Caucasian subjects. Six tagging SNPs and resultant haplotypes were tested for associations with hypertension risk, followed by mean arterial pressure (MAP), plasma renin activity (PRA) and the change in MAP in response to angiotensin II infusion (AngII ΔMAP). The A allele of SNP rs6693954 and the haplotype containing rs6696954A were significantly associated with higher risk for hypertension (OR=1.98, P=0.0001; OR=1.63 P=0.0005, respectively). The same haplotype block was also associated with altered PRA levels and blunted AngII ΔMAP (global P value=0.02, 0.047, respectively). Our results confirm that polymorphisms in the REN are associated with increased risk for hypertension in an independent cohort, and that the underlying mechanism may reside in the interaction of renin activity and vascular responsiveness to angiotensin II.

Associations of genetic polymorphisms in the renin-angiotensin system with central aortic and ambulatory blood pressure in type 2 diabetic patients

“…Among men, on the other hand, the AA carriers had slightly higher central diastolic BP as well as higher AIx, compared to T allele carriers. One previous study in non-diabetic subjects has reported that the renin rs6693954 A allele is associated with a higher risk for hypertension, 17 which is in line with our findings in male diabetic patients. The same study also reported an association of the haplotype containing the renin rs6693954 A allele with plasma renin levels and vascular response to ang II.…”

Lysine-specific demethylase-1 modifies the age effect on blood pressure sensitivity to dietary salt intake

“…The institutional review board of each institution approved the study, and all study participants gave written informed consent prior to enrollment. Results from the HyperPATH cohort have been reported previously (Underwood et al 2010;Sun et al 2011); however, the current analyses are novel and have not been published before.…”

The C4280A (rs5705) gene polymorphism of the renin (REN) gene is associated with risk of developing coronary artery disease, but not with restenosis after coronary stenting

“…Sun et al,studied two [rs5705 (C4280A) and rs10900555 in the intron 1] REN gene polymorphisms and reported the association of the "AA" haplotype with risk of hypertension (Sun et al, 2011). Unfortunately, in the literature there is no evidence of functional studies of the REN polymorphisms.…”

“…Association studies of this polymorphism with some pathologies are very scarce and controversial. Sun et al, reported association of this polymorphism with hypertension in a Caucasian population (Sun et al, 2011), whereas Vefring et al, did not detect association with preeclampsia in mother-father-child triads of preeclampsia pregnancies in a Norway population (Vefring et al, 2010).…”