EVALUATION OF THE SA LOCUS IN HUMAN HYPERTENSION

The SA gene is expressed at 10-fold greater levels in the kidney of th e spontaneously hypertensive rat compared with the normotensive Wistar -Kyoto rat. The gene is linked to blood pressure levels in a number of crosses involving the spontaneously hypertensive rat and other strain s of genetically hypertensive rats. To assess its role in human hypert ension, a human SA cDNA was cloned from a liver library. The cDNA was 1513 bp in length and exhibited a high identity with the published rat SA cDNA sequence in the coding region. A microsatellite marker was de veloped from a yeast artificial chromosome clone containing SA and map ped by linkage to human chromosome 16p13.11-12.3. Polymerase chain rea ction amplification of human genomic DNA revealed two introns located in the SA gene, one of which contains a frequent polymorphism due to a single nucleotide substitution (cytosine to thymidine at residue 79 o f the intron). Association and linkage studies in a large sample of hy pertensive patients, normotensive control subjects, and multiplex sibs hips with these markers and other microsatellites in close proximity t o SA revealed no evidence favoring involvement of the gene in the dise ase in humans. The methodology used in this study can be applied to th e evaluation of other novel candidate genes obtained from investigatio ns of experimental models of hereditary hypertension.