Baroreflex sensitivity and variants of the renin angiotensin system genes

OBJECTIVES Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations b etween baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND Wide intersubject variability in BRS is not well explained by ca rdiovascular risk factors or life style, suggesting a genetic component res ponsible for the variation of BRS. METHODS Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sampl e of 161 women and 154 men aged 41 to 61 years and then in an independent r andom cohort of 29 men and 37 women aged 36 to 37 years. An insertion/delet ion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T varian ts of angiotensinogen (AGT) and two diallelic polymorphisms in the gene enc oding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms mm H g-(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms mm Hg-(=1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), bur not in men. No comparable associ ations were found for BRS with the I/D polymorphism of ACE or the M235T var iant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statisti cally significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS Common genetic polymorphisms in the aldosterone synthase (CYP11 B2) gene is associated with interindividual variation in BRS. (C) 1999 by t he American College of Cardiology.