HUMAN SA GENE LOCUS AS A CANDIDATE LOCUS FOR ESSENTIAL-HYPERTENSION

We have recently identified a candidate gene for rat genetic hypertens ion by identifying an mRNA species that shows markedly higher expressi on in the kidneys of spontaneously hypertensive rats than in those of Wistar-Kyoto rats. By using a restriction fragment length polymorphism , we carried out cosegregation analyses between the genotype of the SA gene and blood pressure in three F-2 cohorts and observed significant effects of the SA gene on blood pressure in all of those cohorts. In the present study, we have isolated a human counterpart of the rat SA gene to investigate the possible association between the human SA gene and human essential hypertension. The deduced amino acid sequence fro m the isolated human SA cDNA consisted of 578 amino acid residues and had slight homology to a bacterial enzyme, acetyl-coenzyme A synthase. The human gene was mapped to the human chromosome 16 with the use of a rodent/human somatic hybrid cell panel. A restriction fragment lengt h polymorphism was found with the restriction enzyme Pst I, and the al lele frequencies were compared between hypertensive and control groups . The hypertensive group consisted of 89 individuals, and the Pst I ra re allele (A2 allele) frequency in this group was 0.270. The control g roup consisted of 81 healthy normotensive individuals whose precise cl inical data were available; the A2 allele frequency in this group was 0.09. Significant differences in the frequency of the A2 allele were o bserved between the hypertensive and control groups (P=.0001). The pre sent findings provide favorable evidence that the SA gene is a candida te gene for human essential hypertension and also provide a starting p oint for future studies.