1. Hypertension. 2004 Nov;44(5):695-701. Epub 2004 Sep 27.
Mapping the genetic determinants of hypertension, metabolic diseases, and related
phenotypes in the lyon hypertensive rat.
Bilusic M(1), Bataillard A, Tschannen MR, Gao L, Barreto NE, Vincent M, Wang T,
Jacob HJ, Sassard J, Kwitek AE.
Author information:
(1)Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226,
USA.
The complex nature of hypertension makes identifying the pathophysiology and its
genetic contributions a challenging task. One powerful approach for the genetic
dissection of blood pressure regulation is studying inbred rat models of
hypertension, as they provide natural allele variants but reduced heterogeneity
(both genetic and etiologic). Furthermore, the detailed physiologic studies to
which the rat is amenable allow for the determination of intermediate phenotypes.
We have performed a total genome scan in offspring of an F2 intercross between
the Lyon hypertensive (LH) and Lyon normotensive rat strains to identify linkage
of anthropometric, blood pressure, renal, metabolic, and endocrine phenotypes.
Quantitative trait locus (QTL) regions involved in blood pressure regulation,
end-stage organ damage, body and organ weight, and lipid metabolism in the LH rat
were identified on chromosomes 1, 2, 3, 5, 7, 10, 13, and 17, with 2 phenotypes
associated with the metabolic syndrome identified on chromosomes 1 and 17.
Regions on chromosomes 2, 13, and 17 were revealed to be important for blood
pressure regulation. Regions on chromosome 17 were found to significantly
contribute to both metabolic homeostasis and blood pressure regulation; 2
aggregates of a total of 23 QTLs were identified, including several "intermediate
phenotypes." These intermediate phenotypes may be used as closer surrogates to
the mechanisms leading to hypertension and metabolic dysfunction in the LH rat.
PMID: 15452030 [PubMed - indexed for MEDLINE]
PUBMED: 15452030
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