Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function

Markku Kupari, Aarno Hautanen, Laura Lankinen, Pekka Koskinen, Juha Virolainen, Heli Nikkila, Perrin C. White

Research output: Contribution to journalArticle

202 Citations (Scopus)

Abstract

Background - Aldosterone has direct and indirect effects on the heart, and genetic variations in aldosterone synthesis could therefore influence cardiac structure and function. Such variations might be associated with polymorphisms in the gene encoding aldosterone synthase (CYP11B2), the enzyme catalyzing the last steps of aldosterone biosynthesis. Methods and Results - A Finnish population sample of 84 persons (44 women) aged 36 to 37 years was studied by M-mode and Doppler echocardiography to assess left ventricular size, mass, and function. Subjects were genotyped through the use of the polymerase chain reaction for two diallelic polymorphisms in CYP11B2: one in the transcriptional regulatory region (promoter) and the other in the second intron. In multiple regression analyses, the CYP11B2 promoter genotype predicted statistically significant variations in left ventricular end- diastolic diameter (β=.40, P<.0001), end-systolic diameter (β=.33, P=.0009), and mass (β=.17, P=.023). These effects were independent of potentially confounding factors, including sex, body size, blood pressure, physical activity, smoking, and ethanol consumption. Genotype groups also differed in a measure of left ventricular diastolic function, the heart rate- adjusted atrial filling fraction (P=.018). Increased dietary salt, which is known to predict increased left ventricular mass, had this effect only in association with certain CYP11B2 genotypes (P<.001). Conclusions - Genetic variations in or near the aldosterone synthase (CYP11B2) gene strongly affect left ventricular size and mass in young adults free of clinical heart disease. These polymorphisms may also influence the response of the left ventricle to increases in dietary salt.

Original languageEnglish (US)
Pages (from-to)569-575
Number of pages7
JournalCirculation
Volume97
Issue number6
StatePublished - 1998

Fingerprint

Cytochrome P-450 CYP11B2
Genes
Aldosterone
Genotype
Salts
Sex Factors
Doppler Echocardiography
Nucleic Acid Regulatory Sequences
Body Size
Left Ventricular Function
Introns
Heart Ventricles
Echocardiography
Young Adult
Heart Diseases
Ethanol
Heart Rate
Smoking
Regression Analysis
Exercise

Keywords

  • Echocardiography
  • Genes
  • Ventricles

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Kupari, M., Hautanen, A., Lankinen, L., Koskinen, P., Virolainen, J., Nikkila, H., & White, P. C. (1998). Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation, 97(6), 569-575.

Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. / Kupari, Markku; Hautanen, Aarno; Lankinen, Laura; Koskinen, Pekka; Virolainen, Juha; Nikkila, Heli; White, Perrin C.

In: Circulation, Vol. 97, No. 6, 1998, p. 569-575.

Research output: Contribution to journalArticle

Kupari, M, Hautanen, A, Lankinen, L, Koskinen, P, Virolainen, J, Nikkila, H & White, PC 1998, 'Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function', Circulation, vol. 97, no. 6, pp. 569-575.
Kupari M, Hautanen A, Lankinen L, Koskinen P, Virolainen J, Nikkila H et al. Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation. 1998;97(6):569-575.
Kupari, Markku ; Hautanen, Aarno ; Lankinen, Laura ; Koskinen, Pekka ; Virolainen, Juha ; Nikkila, Heli ; White, Perrin C. / Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. In: Circulation. 1998 ; Vol. 97, No. 6. pp. 569-575.
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AU - Kupari, Markku

AU - Hautanen, Aarno

AU - Lankinen, Laura

AU - Koskinen, Pekka

AU - Virolainen, Juha

AU - Nikkila, Heli

AU - White, Perrin C.

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N2 - Background - Aldosterone has direct and indirect effects on the heart, and genetic variations in aldosterone synthesis could therefore influence cardiac structure and function. Such variations might be associated with polymorphisms in the gene encoding aldosterone synthase (CYP11B2), the enzyme catalyzing the last steps of aldosterone biosynthesis. Methods and Results - A Finnish population sample of 84 persons (44 women) aged 36 to 37 years was studied by M-mode and Doppler echocardiography to assess left ventricular size, mass, and function. Subjects were genotyped through the use of the polymerase chain reaction for two diallelic polymorphisms in CYP11B2: one in the transcriptional regulatory region (promoter) and the other in the second intron. In multiple regression analyses, the CYP11B2 promoter genotype predicted statistically significant variations in left ventricular end- diastolic diameter (β=.40, P<.0001), end-systolic diameter (β=.33, P=.0009), and mass (β=.17, P=.023). These effects were independent of potentially confounding factors, including sex, body size, blood pressure, physical activity, smoking, and ethanol consumption. Genotype groups also differed in a measure of left ventricular diastolic function, the heart rate- adjusted atrial filling fraction (P=.018). Increased dietary salt, which is known to predict increased left ventricular mass, had this effect only in association with certain CYP11B2 genotypes (P<.001). Conclusions - Genetic variations in or near the aldosterone synthase (CYP11B2) gene strongly affect left ventricular size and mass in young adults free of clinical heart disease. These polymorphisms may also influence the response of the left ventricle to increases in dietary salt.

AB - Background - Aldosterone has direct and indirect effects on the heart, and genetic variations in aldosterone synthesis could therefore influence cardiac structure and function. Such variations might be associated with polymorphisms in the gene encoding aldosterone synthase (CYP11B2), the enzyme catalyzing the last steps of aldosterone biosynthesis. Methods and Results - A Finnish population sample of 84 persons (44 women) aged 36 to 37 years was studied by M-mode and Doppler echocardiography to assess left ventricular size, mass, and function. Subjects were genotyped through the use of the polymerase chain reaction for two diallelic polymorphisms in CYP11B2: one in the transcriptional regulatory region (promoter) and the other in the second intron. In multiple regression analyses, the CYP11B2 promoter genotype predicted statistically significant variations in left ventricular end- diastolic diameter (β=.40, P<.0001), end-systolic diameter (β=.33, P=.0009), and mass (β=.17, P=.023). These effects were independent of potentially confounding factors, including sex, body size, blood pressure, physical activity, smoking, and ethanol consumption. Genotype groups also differed in a measure of left ventricular diastolic function, the heart rate- adjusted atrial filling fraction (P=.018). Increased dietary salt, which is known to predict increased left ventricular mass, had this effect only in association with certain CYP11B2 genotypes (P<.001). Conclusions - Genetic variations in or near the aldosterone synthase (CYP11B2) gene strongly affect left ventricular size and mass in young adults free of clinical heart disease. These polymorphisms may also influence the response of the left ventricle to increases in dietary salt.

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