A high prevalence of Gitelman's syndrome mutations in Japanese

Hypertens Res. 2004 May;27(5):327-31. doi: 10.1291/hypres.27.327.


Although Gitelman's syndrome (GS) is considered a rare disorder, it is an autosomal recessive phenotype and the frequency of heterozygote subjects might be higher than suspected. The purpose of this study was to assess the prevalence of GS in Japanese and the effects of heterozygous GS mutations on blood pressure levels. We used the TaqMan system to detect 9 Gitelman's syndrome mutations in SLC12A3 that have been reported in Japanese. We then conducted association studies between these mutations and blood pressure in 1,852 subjects recruited from the Suita study, representing the general population in Japan. Among these 1,852 subjects, we detected the T180K, A569V, L623P, R642C, and L849H heterozygote genotypes in 56, 14, 1, 1, and 47 subjects, respectively. The overall frequency of GS mutations was (56+14+1+1+47) / (1,852 x 2) = 0.0321, which was much higher than suspected. This means we should expect to find one subject with a heterozygous GS mutation among 15.6 Japanese or that we should find 10.3 GS subjects among 10,000 Japanese. Although the blood pressure levels of subjects heterozygous for the T180K, A569V, or L849H genotype were not significantly different from those of wild-type subjects, urine pH in subjects with GS mutations was significantly higher than that in subjects without mutations. In conclusion, GS could be one of the major causes of low blood pressure in Japanese.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group / genetics*
  • Asian Continental Ancestry Group / statistics & numerical data
  • Blood Pressure
  • Carrier Proteins / genetics*
  • Gene Frequency
  • Genes, Recessive*
  • Genotype
  • Heterozygote
  • Humans
  • Hydrogen-Ion Concentration
  • Japan / epidemiology
  • Kidney Diseases / epidemiology
  • Kidney Diseases / genetics*
  • Kidney Diseases / physiopathology
  • Kidney Diseases / urine
  • Kidney Tubules*
  • Middle Aged
  • Mutation*
  • Prevalence
  • Receptors, Drug / genetics*
  • Sodium Chloride Symporters
  • Solute Carrier Family 12, Member 3
  • Symporters*
  • Urine / chemistry


  • Carrier Proteins
  • Receptors, Drug
  • SLC12A3 protein, human
  • Sodium Chloride Symporters
  • Solute Carrier Family 12, Member 3
  • Symporters
  • thiazide receptor