Evaluation of the SA locus in human hypertension

The SA gene is expressed at 10-fold greater levels in the kidney of the 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 strains of genetically hypertensive rats. To assess its role in human hypertension, 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 developed from a yeast artificial chromosome clone containing SA and mapped by linkage to human chromosome 16p13.11-12.3. Polymerase chain reaction 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 of the intron). Association and linkage studies in a large sample of hypertensive patients, normotensive control subjects, and multiplex sibships with these markers and other microsatellites in close proximity to SA revealed no evidence favoring involvement of the gene in the disease in humans. The methodology used in this study can be applied to the evaluation of other novel candidate genes obtained from investigations of experimental models of hereditary hypertension.