gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Norepinephrine Transporter (NET) Gene and Cardiovascular Regulation: a twin analysis

Noradrenalin Transporter Gen und kardiovaskuläre Regulation: Eine Zwillingsanalyse

Meeting Abstract (Hypertonie 2004)

Suche in Medline nach

  • J. Jordan - Franz-Volhard Clinical Research Center, Charité (Berlin, D)
  • A. Aydin - Franz-Volhard Clinical Research Center, Charité (Berlin, D)
  • F.C. Luft - Franz-Volhard Clinical Research Center, Charité (Berlin, D)
  • A. Busjahn - Healthtwist GmbH (Berlin, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP125

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch125.shtml

Veröffentlicht: 10. August 2005

© 2005 Jordan et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Background: The norepinephrine transporter has a central role in the regulation of synaptic norepinephrine concentrations. Rare mutations of the NET gene are associated with abnormalities in cardiovascular regulation, such as orthostatic tachycardia.

Methods: We tested the hypothesis that the NET gene locus contributes to variability in cardiovascular regulation in healthy monozygotic and dizygotic twin pairs. Subjects underwent a cardiovascular evaluation including cold-pressor and handgrip testing and determination of plasma catecholamine concentrations in the supine position. ECG, beat-by-beat blood pressure, and brachial blood pressure were monitored continuously. We then conducted an identity-by-decent linkage analysis with NET gene locus in 62 dizygotic twins and their parents. Furthermore we genotyped 23 single nucleotide polymorphisms (SNP) in the NET regulatory and coding regions in the same twins plus 94 single members of the monozygotic twin pairs. Linkage analysis was done with maximum likelihood estimations; association was tested by ANOVA.

Results: We found significant linkage (p=0.0005) between the NET gene locus and plasma epinephrine concentrations, as well as a tendency for linkage with heart rate change during cold pressor and handgrip testing. We observed a significant association between six SNP's and plasma epinephrine concentrations (p=0.01to p=0.05). The association analysis was also significant for, both blood pressure changes with handgrip (6 SNP's) and cold pressor testing (2 SNP's). Linkage and association analysis were negative for plasma norepinephrine concentrations.

Conclusions: Our study suggests that the NET gene contributes to the variability in cardiovascular regulation and catecholamine turnover in the general population. Given the large number of polymorphisms in the NET gene, haplotype analyses in larger sample sizes will be necessary to confirm these findings