The gene for the β-subunit of the epithelial sodium channel (βENaC) is one of the most prominent candidate genes being analyzed for an association with human essential hypertension. It is known that a deletion or alteration of PY motif in exon 12 of βENaC is responsible for Liddle's syndrome. Although the localization of genetic polymorphisms of βENaC is unique to each population, intensive analysis of individuals of white and African ancestry has demonstrated that genetic variants are localized in exons 8 and 12, with two frequent polymorphisms, G442V in exon 8 and T594M in exon 12. These two mutations are both found in individuals of African ancestry, and might be associated with elevated blood pressure (BP). Previously, we have screened the last two-thirds of exon 12 in the Japanese population, and demonstrated the absence of the T594M mutation and the presence of a novel P592S mutation. In the present study, we further examined the rest of exon 12 and exon 8 in a general population from Ohasama, Japan (the Ohasama Study), using single-strand conformational polymorphism (SSCP) analysis. We screened 803 subjects randomly selected from the representative participants, who measured their home and casual BP. The PCR products presenting a shift in SSCP gels, as well as controls, were directly sequenced by autoanalyzer to identify the mutation. A novel gel shift was noted in exon 12 (n = 8) and sequencing identified a polymorphism at codon Ser 520, leading to no change in amino acid sequence (G77576C TCG→TCC). In exon 8, all three SSCP variants were heterogynous for V434M (GTG→ATG), which is coincident with a rare polymorphism in whites. The G442V mutation, however, was absent from the Japanese population. A novel mutation of exon 12 was not associated with a significant difference in clinical features. These results indicate that Japanese people possess three polymorphisms in exon 12, all of which are unique, and one in exon 8. These genetic variants of βENaC may not influence the BP level of Japanese people.
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