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CLINICAL STUDIES

Baroreflex sensitivity and variants of the renin angiotensin system genes

Antti Ylitalo, MD^*, K. E. Juhani Airaksinen, MD^* , Aarno Hautanen, MD, Markku Kupari, MD, Marion Carson, MD, Juha Virolainen, MD, Markku Savolainen, MD, Heikki Kauma, MD, Y. Antero Kesäniemi, MD, Perrin C. White, MD and Heikki V. Huikuri, MD, FACC^*

^* Division of Cardiology, Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
Atherosclerosis Research Group, Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Manuscript received July 29, 1999; revised manuscript received August 23, 1999, accepted September 21, 1999.

Reprint requests and correspondence: Dr. Heikki Huikuri, Division of Cardiology, Department of Medicine, University of Oulu, Kajaanintie 50, FIN-90220 Oulu, Finland.
heikki.huikuri{at}oulu.fi

OBJECTIVES

Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes.

BACKGROUND

Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible 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 sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding 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 Hg^–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), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03).

CONCLUSIONS

Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   AGT = angiotensinogen   ANOVA = analysis of variance   BP = blood pressure   BRS = baroreflex sensitivity   CYP11B2 = aldosterone synthase   I/D = insertion/deletion   PCR = polymerase chain reaction   RAS = renin-angiotensin-aldosterone system   SD = standard deviation

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