Background. Mutations have been found only in exons 8 and 12 of the β-subunit of the epithelial sodium channel (βENaC), but the presence of other mutations in the remaining exons remains to be determined in the Japanese population. New cases with the V434M mutation should be identified because the identified individuals have high plasma sodium concentration. Methods. Exons 1 to 7 and 9 to 11 were screened by using single-strand conformational polymorphism (SSCP) in 200 subjects (100 normotensive and 100 hypertensive) randomly selected from 1245 participants in a community-based cohort study (Ohasama study) in northern Japan. Results. Four novel mutations were detected in exons 5, 6, and 7, and one of them was the novel missense mutation, P369H in exon 6. Then extended investigation of this mutation, together with those of V434M and P592S, which were identified in our previous studies, was performed in 1245 subjects. The final frequency of these mutations was 1/1245 for P369H, 5/1245 for V434M, and 5/1245 for P592S. Although a significant association with hypertension was not achieved, 3 of the 5 subjects with V434M were diagnosed as hypertensive. Plasma sodium concentrations were significantly high and plasma renin activity tended to be low in subjects with V434M. The only subject with P369H showed slightly elevated diastolic pressure, but no other abnormal characteristics were noted in the subjects with P369H or P592S. Conclusions. Genetic polymorphisms of βENaC in the Japanese population were determined. Clinical features in those with the V434M mutation suggest the presence of physiological effects of this mutation on plasma sodium regulation.
- Epithelial sodium channel
- Plasma sodium