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Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension
Michal Pravenec, … , Elizabeth M. St. Lezin, Theodore W. Kurtz
Michal Pravenec, … , Elizabeth M. St. Lezin, Theodore W. Kurtz
Published June 15, 1999
Citation Information: J Clin Invest. 1999;103(12):1651-1657. https://doi.org/10.1172/JCI6691.
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Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension

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Abstract

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR.BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR.BN-Il6/Npy strain.

Authors

Michal Pravenec, Vaclav Zidek, Miroslava Simakova, Vladimir Kren, Drahomira Krenova, Karel Horky, Marie Jachymova, Blanka Mikova, Ludmila Kazdova, Timothy J. Aitman, Paul C. Churchill, R. Clinton Webb, Nilesh H. Hingarh, Ying Yang, Jia-Ming Wang, Elizabeth M. St. Lezin, Theodore W. Kurtz

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Figure 1

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Linkage map of chromosome 4. Linkage map showing the transferred segment...
Linkage map of chromosome 4. Linkage map showing the transferred segment of chromosome 4 in the SHR.BN-Il6/Npy congenic strain. The filled bar denotes the chromosome region from the BN strain that has been fixed in the homozygous state on the SHR background. The cross-hatched bar denotes region in which some residual heterozygosity may exist within the congenic strain. The open region denotes the flanking segment of SHR chromosome. Map distances are adapted from chromosome 4 maps of the WIBR/MIT Rat Genome Center (17), Jacob et al. (30), and Pravenec et al. (31). The position of Cd36 is based on radiation hybrid mapping results of Aitman et al. (13).

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