Baroreflex sensitivity and variants of the renin angiotensin system genes

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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)194-200
Number of pages7
JournalJournal of the American College of Cardiology
Volume35
Issue number1
DOIs
StatePublished - Jan 2000

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Baroreflex
Cytochrome P-450 CYP11B2
Renin-Angiotensin System
Genes
Genotype
Angiotensinogen
Peptidyl-Dipeptidase A
Genetic Polymorphisms
Introns
Valsalva Maneuver
Population
Life Style
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Nursing(all)

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Ylitalo, A., Juhani Airaksinen, K. E., Hautanen, A., Kupari, M., Carson, M., Virolainen, J., ... Huikuri, H. V. (2000). Baroreflex sensitivity and variants of the renin angiotensin system genes. Journal of the American College of Cardiology, 35(1), 194-200. https://doi.org/10.1016/S0735-1097(99)00506-9

Baroreflex sensitivity and variants of the renin angiotensin system genes. / Ylitalo, Antti; Juhani Airaksinen, K. E.; Hautanen, Aarno; Kupari, Markku; Carson, Marion; Virolainen, Juha; Savolainen, Markku; Kauma, Heikki; Antero Kesäniemi, Y.; White, Perrin C.; Huikuri, Heikki V.

In: Journal of the American College of Cardiology, Vol. 35, No. 1, 01.2000, p. 194-200.

Research output: Contribution to journalArticle

Ylitalo, A, Juhani Airaksinen, KE, Hautanen, A, Kupari, M, Carson, M, Virolainen, J, Savolainen, M, Kauma, H, Antero Kesäniemi, Y, White, PC & Huikuri, HV 2000, 'Baroreflex sensitivity and variants of the renin angiotensin system genes', Journal of the American College of Cardiology, vol. 35, no. 1, pp. 194-200. https://doi.org/10.1016/S0735-1097(99)00506-9
Ylitalo A, Juhani Airaksinen KE, Hautanen A, Kupari M, Carson M, Virolainen J et al. Baroreflex sensitivity and variants of the renin angiotensin system genes. Journal of the American College of Cardiology. 2000 Jan;35(1):194-200. https://doi.org/10.1016/S0735-1097(99)00506-9
Ylitalo, Antti ; Juhani Airaksinen, K. E. ; Hautanen, Aarno ; Kupari, Markku ; Carson, Marion ; Virolainen, Juha ; Savolainen, Markku ; Kauma, Heikki ; Antero Kesäniemi, Y. ; White, Perrin C. ; Huikuri, Heikki V. / Baroreflex sensitivity and variants of the renin angiotensin system genes. In: Journal of the American College of Cardiology. 2000 ; Vol. 35, No. 1. pp. 194-200.
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AU - Ylitalo, Antti

AU - Juhani Airaksinen, K. E.

AU - Hautanen, Aarno

AU - Kupari, Markku

AU - Carson, Marion

AU - Virolainen, Juha

AU - Savolainen, Markku

AU - Kauma, Heikki

AU - Antero Kesäniemi, Y.

AU - White, Perrin C.

AU - Huikuri, Heikki V.

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N2 - 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.

AB - 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.

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