Salt sensitivity of Japanese from the viewpoint of gene polymorphism.

Excess salt intake is an important environmental risk for the predisposition to essential hypertension. Previous physiological studies have shown that salt sensitivity is associated with insulin resistance, enhancement of sympathetic nerve activity and decrease of blood pressure decline at night. We have been examining the genetic importance of candidate gene polymorphisms of salt-sensitive hypertension using several populations. The angiotensinogen gene (AGT) is a thrifty gene which increases the risk for common disease with growth of civilization via sodium and body fluid retention. The CC genotype of the AGT/T+31C polymorphism, which is in complete linkage disequilibrium with the TT genotype of the M235T polymorphism, was associated with a decrease of blood pressure decline at night in the Ohasama Study. On the other hand, the Gly460Trp genotype of the alpha-adducin gene (ADD1) is associated with erythrocyte sodium transport and increases tubular sodium reabsorption and risk for hypertension. We also revealed in the Ohasama Study that the Trp460 allele of ADD1 is associated with hypertension in young subjects with low renin activity. In addition to these polymorphisms, the T(-344)C polymorphism in the promoter of the aldosterone synthase gene (CYP11B2) and the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) are considered candidates for the genetic risk of salt-sensitive hypertension. We compared the allele frequency of five candidate genes between Japanese and Caucasians; the results showed that the frequencies of all alleles were significantly higher in Japanese than in Caucasians. This interesting finding might suggest a feasible explanation for the huge interracial differences in the frequency of salt-sensitive hypertension.