Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension

Disorders of carbohydrate and lipid metabolism have been reported to cluste r 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 adip ocytes from SHRs, However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unkn own. In the SHR.BN-I16/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway(BN) rat on to the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglycerid emia. These results demonstrate that a single chromosome region can influen ce a broad spectrum of cardiovascular risk factors involved in the hyperten sion metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was n ot critical to the initial selection for hypertension in the SHR model. Thu s, the ability of chromosome 4 to influence multiple cardiovascular risk fa ctors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR.BN-I16/Npy strain.