Faculty Collaboration Database

Mapping the genetic determinants of hypertension, metabolic diseases, and related phenotypes in the lyon hypertensive rat. Hypertension 2004 Nov;44(5):695-701

Date

09/29/2004

Pubmed ID

15452030

DOI

10.1161/01.HYP.0000144542.57306.5e

Scopus ID

2-s2.0-7444254076 (requires institutional sign-in at Scopus site)   49 Citations

Abstract

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.

Author List

Bilusic M, Bataillard A, Tschannen MR, Gao L, Barreto NE, Vincent M, Wang T, Jacob HJ, Sassard J, Kwitek AE

Authors

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Anthropometry
Blood Pressure
Chromosome Mapping
Chromosomes, Mammalian
Genetic Linkage
Hypertension
Lipid Metabolism
Male
Metabolic Diseases
Models, Animal
Phenotype
Quantitative Trait Loci
Rats
Rats, Inbred Strains