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Angiotensin-Converting Enzyme and Angiotensinogen Gene Polymorphisms and Heart Rate Variability in Twins 1

https://doi.org/10.1016/S0002-9149(97)01019-9Get rights and content

Abstract

Decreased heart rate variability (HRV) is associated with congestive heart failure, post-myocardial infarction, ventricular arrhythmias, sudden cardiac death, and advancing age. A deletion/insertion polymorphism in the angiotensin-converting enzyme (ACE) gene and a substitution (M235T) in the angiotensinogen gene have been associated with risk for heart disease. The aim of this study was to determine the heritability of HRV and related parameters in monozygotic and dizygotic twins and to assess the influence of ACE and angiotensinogen polymorphisms. We studied 95 MZ pairs and 46 DZ pairs. We measured HRV and related parameters, ACE and angiotensinogen levels, plasma norepinephrine, ACE, and angiotensinogen genotypes. We found that HRV and related parameters were significantly influenced by genetic variability, although nonshared genetic effects were also important. Angiotensinogen and plasma norepinephrine were generally correlated with decreased HRV, whereas ACE was correlated with perturbances of normal rhythmic HRV. Nevertheless, the DD ACE genotype was associated with increased HRV (p <0.05), whereas angiotensinogen polymorphisms had no effect. We conclude that HRV and related parameters are in part heritable. Interestingly, the DD ACE genotype is associated with increased HRV.

Section snippets

Methods

We recruited 141 pairs of MZ (95 pairs) and DZ (46 pairs) twins by advertisement (print media) to participate in studies involving blood pressure and blood pressure reactivity to physical and mental stress.[9]The subjects were all German Caucasians. They were recruited from various parts of Germany, which minimizes any regional effects. The protocol was approved by the University’s committee on the protection of human subjects and written informed consent was obtained from all participants.

Results

Table I lists demographic data on all subjects divided into ACE genotypes. The ACE genotype had a significant effect on plasma ACE levels; the D allele conferred a higher ACE level. The ACE genotype also had an effect on angiotensinogen levels. Persons with the DD ACE genotype had lower angiotensinogen levels. Table II lists the correlation coefficients between HRV parameters and blood pressure, heart rate, plasma norepinephrine, ACE activity, and angiotensinogen in the entire cohort. Only

Discussion

The important findings in this study are that HRV and related parameters show correlations with blood pressure, heart rate, plasma norepinephrine, angiotensinogen, and ACE levels. HRV and related parameters are heritable, and are more pronounced in persons carrying the ACE intron 16 DD genotype than in those possessing the I allele. We found no genetic association between HRV and the angiotensinogen locus. From the heritability estimates, we concluded that genetic influences on HRV were mostly

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    1

    This study was supported in part by a grant-in-aid from the BMBF LPD 1995; by a grant-in-aid from the Bundesministerium ü Bildung und Forschung; and by Vo 505/2-1 from the Deutsche Forschungsgemeinschaft, Bonn, Germany.

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