[Mutational analysis of a thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in a Japanese population--the Iwaki Health Promotion Project].

Mutations in the thiazide-sensitive Na-Cl cotransporter (SLC12A3) are considered to cause Gitelman's syndrome (GS), an autosomal recessive inherited renal tubular disorder. In the present study, to assess the prevalence of 3 SLC12A3 missense mutations(T180K, L849H, and R919C), involving community-based subjects with hypokalemia, mutation analysis was performed in 1567 subjects in Aomori Prefecture, a northern part of Japan. All subjects were participants in the Iwaki Health Promotion Project. Genotypes of the SLC12A3 mutations were determined by the TaqMan PCR method. Among these 1567 subjects, we detected missense mutations of T180K, L849H, and R919C in 40, 49, and 57 subjects, respectively. One subject had a homozygous (L849H) and heterozygous (R919C) mutation. Two subjects had homozygous mutations (R919C). Five subjects had compound heterozygous mutations: 2 subjects with T180K and R919C, one subject with T180K and R919C, and 2 subjects with L849H and R919C. One hundred and thirty-two subjects had a heterozygous mutation, and 1427 subjects had no mutations. The overall frequency of GS mutations was 8.9%. The mutant allele frequency of T180K, L849H, and R919C was 1.3, 1.6, and 1.9%, respectively. The GS mutant allele frequency of the 1,567 Japanese was more than 4.8%. The present study revealed that the allele frequency of these GS mutations was 4.8% in a Japanese population. In addition, these findings suggest that the allele frequency of GS mutations may be higher than expected, although GS is considered to be a rare disorder.