Renal disease susceptibility and hypertension are under independent genetic control in the fawn-hooded rat.
Hypertension, diabetes and hyperlipidemia are risk factors for life-threatening complications such as end-stage renal disease, coronary artery disease and stroke. Why some patients develop complications is unclear, but only susceptibility genes may be involved. To test this notion, we studied crosses involving the fawn-hooded rat, an animal model of hypertension that develops chronic renal failure. Here, we report the localization of two genes, Rf-1 and Rf-2, responsible for about half of the genetic variation in key indices of renal impairment. In addition, we localize a gene, Bpfh-1, responsible for about 26% of the genetic variation in blood pressure. Rf-1 strongly affects the risk of renal impairment, but has no significant effect on blood pressure. Our results show that susceptibility to a complication of hypertension is under at least partially independent genetic control from susceptibility to hypertension itself.
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
D M
DM
Brown
A P
AP
Provoost
M J
MJ
Daly
E S
ES
Lander
H J
HJ
Jacob
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D008040:Genetic Linkage; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D011507:Proteinuria / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains / Q000235:genetics*; D051437:Renal Insufficiency / Q000235:genetics*
D017931:DNA Primers