gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Different genetic loci are involved in the development of salt-independent early onset albuminuria and in salt-dependent progressive renal damage

Alters- und Diätabhängige genetische Beeinflussung der Nierenschädigung bei salzsensitiver Hypertonie

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker A.K. Siegel - Charité Universitätsmedizin Berlin (Berlin, D)
  • A. Mehr Poyan - Charité Universitätsmedizin Berlin (Berlin, D)
  • M. Planert - Charité Universitätsmedizin Berlin (Berlin, D)
  • A. Schulz - Charité Universitätsmedizin Berlin (Berlin, D)
  • R. Kreutz - Charité Universitätsmedizin Berlin (Berlin, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP37

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2003/03hoch137.shtml

Veröffentlicht: 11. November 2004

© 2004 Siegel 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

Text

Salt-sensitive hypertension (SS-HTN) is a major health issue due to its high prevalence and the associated pronounced target organ damage. Familial aggregation and the higher proportion in specific ethnic populations argue for the involvement of genetic factors in SS-HTN. To identify the genetic basis for the manifestation and progression of renal damage in SS-HTN we performed linkage analysis between 2 inbred genetic rat strains with similar spontaneous hypertension but disparate genetic susceptibility to salt-induced disease progression.

We studied F2-progeny of a salt-resistant spontaneously hypertensive rat (SHR) strain and the contrasting salt-sensitive hypertensive Dahl rat (SS) at different times of age and under low (0.2% NaCl) and high salt (4% NaCl) diet. Measurement of urinary albumin excretion (UAE) as a marker of renal damage, was done in 230 male F2-animals at the age of 14 weeks after 8 weeks of high salt diet and in 539 young male F2-animals at the age of 8 weeks on low salt conditions.

In both crosses a complete genome screen was performed on all rat chromosomes (RNO) except the Y chromosome. QTL mapping for the low salt-animals detected 8 QTL with significant or suggestive linkage for UAE on RNO 2, 6, 8, 9, 10, 11 and 19. Analysis in the high salt-animals revealed 3 QTLs in the same or colocalized chromosomal region of RNO 8, 9 and 19, whereas the identified QTL on RNO 6 is different from that in the low salt-group.

The salt-independent early onset of UAE in the young animals and the progression of renal damage in SS-HTN is polygenetic determined and regulated by different sets of genetic loci. Interestingly, we identified two independent QTL on RNO 6, one is mainly linked to early onset albuminuria, while the other is linked to progressive renal damage after salt-loading only. Our data point to the importance of age of onset effects and of environmental factors for the development and progression of renal disease in hypertension.

The salt-independent early onset of UAE in the young animals and the progression of renal damage in SS-HTN is polygenetic determined and regulated by different sets of genetic loci. Interestingly, we identified two independent QTL on RNO 6, one is mainly linked to early onset albuminuria, while the other is linked to progressive renal damage after salt-loading only. Our data point to the importance of age of onset effects and of environmental factors for the development and progression of renal disease in hypertension.