Mutational analysis of SLC12A3 gene in a Japanese general population of northern Japan

Abstract

    Gitelman's syndrome (GS) is considered to be a rare disorder. To assess the prevalence of GS in the Japanese general population and the relationships between mutations of related genes and blood pressure, we performed mutational analysis of the SLC12A3 gene on 1,567 subjects from Aomori Prefecture in northern Japan. Three GS mutations in SLC12A3, identified in the subjects with hypokalemia in a preliminary study were assessed by the TaqMan PCR method. We detected T180K, L849H and R919C missense mutations in 40, 49 and 57 subjects, respectively. 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. GS mutant allele frequency in the 1,567 Japanese was more than 4.8%. In addition, subjects with L849H mutation had significantly lower systolic blood pressure when compared to subjects with wild-type SLC12A3 (121.8 ± 18.4 versus 127.8 ± 18.9 mmHg; P < 0.05). In conclusion, the present results suggest that the frequency of GS mutations is unexpectedly high, although GS is considered to be a rare disorder. The results also suggest that loss-of-function in the SLC12A3 via the L849H mutation reduces blood pressure, thereby contributing to resistance to hypertension.