Published Online
on October 10, 2005

A more recent version of this article appeared on December 1, 2005

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Submitted on July 8, 2005
Revised on July 26, 2005

Genome-Wide Scan for Linkage to Obesity-Associated Hypertension in French Canadians

Zdenka Pausova^*; Daniel Gaudet; Francis Gossard; Manon Bernard; Mary L. Kaldunski; Michele Jomphe; Johanne Tremblay; Thomas J. Hudson; Gerard Bouchard; Theodore A. Kotchen; Allen W. Cowley; and Pavel Hamet

From the Brain and Body Centre (Z.P., M.B.), University of Nottingham, United Kingdom; Centre Hospitalier de l’Université de Motréal (Z.P., F.G., M.B., J.T., P.H.), Montreal, Canada; Centre de Médicine Génique Communitaire (D.G.), Chicoutimi, Canada; BALSAC Project (M.J., G.B.), University of Quebec in Chicoutimi, Canada; McGill University and Genome Quebec Innovation Centre (T.J.H.), Montreal, Canada; and Medical College of Wisconsin (M.L.K., T.A.K., A.W.C.), Milwaukee.

^* To whom correspondence should be addressed. E-mail: zdenka.pausova{at}nottingham.ac.uk.

Abstract--Essential hypertension is a heterogeneous disorder that is thought to develop because of several overlapping subsets of underlying mechanisms. One such causal pathway may involve pathophysiological alterations induced by obesity. In the present study, we examined whether investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, facilitates the search for its genes. Fifty-five extended families were selected on the basis of having 2 siblings affected by hypertension from a geographically remote French-Canadian population. Fifteen of these families showed a high prevalence (70%) of obesity. Genome-wide scan using qualitative multipoint linkage analysis (GeneHunter 2.1; marker density <10 cM) was performed in the entire set of hypertensive families and the subset with high prevalence of obesity. In the scan involving all 55 families, the most significant loci (logarithm of odds [LOD] score=2.5) were identified on chromosomes 1 (D1S1597) and 11 (D11S1999). In the scan including only the subset of families with obesity-hypertension, the most significant locus (LOD score=3.1) was found on chromosome 1 in the same region as the scan involving all families (D1S1597). Genotyping additional markers increased the significance of this locus (LOD score=3.5) and refined its position (D1S2672). Several candidate genes of obesity-hypertension are located in close proximity; these include the tumor necrosis factor receptor 2 and atrial natriuretic peptide genes. These results suggest that investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, may facilitate the search for genes of this complex disorder.

Key words: hypertension, obesity • genetics

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