title: Mapping and confirmation of a major left ventricular mass QTL on rat chromosome 1 by contrasting SHRSP and F344 rats.
abstract: An abnormal increase in left ventricular (LV) mass, i.e., LV hypertrophy (LVH), represents an important target organ damage in arterial hypertension and has been associated with poor clinical outcome. Genetic factors are contributing to variation in LV mass in addition to blood pressure and other factors such as dietary salt intake. We set out to map quantitative trait loci (QTL) for LV mass by comparing the spontaneously hypertensive stroke-prone (SHRSP) rat with LVH and normotensive Fischer rats (F344) with contrasting low LV mass. To this end we performed a genome-wide QTL mapping analysis in 232 F2 animals derived from SHRSP and F344 exposed to high-salt (4% in chow) intake for 8 wk. We mapped one major QTL for LV mass on rat chromosome 1 (RNO1) that demonstrated strong linkage (peak logarithm of odds score 8.4) to relative LV weight (RLVW) and accounted for ∼19% of the variance of this phenotype in F2 rats. We therefore generated a consomic SHRSP-1(F344) strain in which RNO1 from F344 was introgressed into the SHRSP background. Consomic and SHRSP animals showed similar blood pressures during conventional intra-arterial measurements, while RLVW was already significantly lower (-17.7%, P<0.05) in SHRSP-1(F344) in response to a normal-salt diet; a similar significant reduction of LV mass was also observed in consomic rats after high-salt intake (P<0.05 vs. SHRSP). Thus, a major QTL on RNO1 was confirmed with significant impact on LV mass in the hypertensive background of SHRSP.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, CharitéCentrum für Therapieforschung, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Grabowski
authors.forename: Gerold
authors.initials: G
authors.lastname: Koplin
authors.forename: Bujar
authors.initials: B
authors.lastname: Aliu
authors.forename: Leonard
authors.initials: L
authors.lastname: Schulte
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D006352:Heart Ventricles / Q000473:pathology*; D006973:Hypertension / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D013045:Species Specificity
keywords: QTL; hypertension; left ventricular hypertrophy; rat