Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure

Nephrol Dial Transplant. 2009 Apr;24(4):1170-5. doi: 10.1093/ndt/gfn619. Epub 2008 Nov 25.


Background: Gitelman's syndrome (GS), which is caused by homozygous or compound heterozygous mutations of the thiazide-sensitive sodium chloride cotransporter (NCC), usually manifests in children and is associated with low blood pressure. However, the prevalence of heterozygous NCC mutations and their association with blood pressure in children have not yet been studied.

Methods: Five hundred unrelated children from the Taipei Children Heart Study were enrolled. Genomic DNA was isolated from peripheral blood and the SLC12A3 gene was amplified by polymerase chain reaction (PCR). The 15 NCC mutations previously identified in Chinese patients with GS were evaluated using restriction fragment length polymorphism (RFLP) analysis. Blood pressure, biochemistry and urine pH were measured. The allelic frequency of heterozygous NCC mutations and their association with low blood pressure were also investigated.

Results: RFLP analysis for the 15 NCC mutations revealed heterozygous T60M in 1 child, T163M in 1, S283Y in 4, R642C in 2, W844X in 2, R928C in 9 and R959frameshift in 10 children. The overall incidence of positive heterozygous NCC mutations was approximately 2.9%. There were no significant differences in systolic or diastolic blood pressure, biochemical profiles or urine pH between children with heterozygous NCC mutations (n = 29) and non-affected controls (n = 471), except for slightly higher fasting plasma glucose concentrations in NCC-heterozygous children (91 +/- 2.3 versus 88 +/- 0.4 mg/dL, P < 0.05). Examination among the different NCC mutations showed that these children also had comparable blood pressures.

Conclusions: We found a relatively high prevalence of heterozygous NCC mutations in Chinese children, suggesting that GS may not be rare in this population. Heterozygous NCC mutations were not associated with lower blood pressure in these Chinese children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asian Continental Ancestry Group
  • Child
  • Female
  • Gene Frequency
  • Gitelman Syndrome / epidemiology
  • Gitelman Syndrome / genetics*
  • Heterozygote
  • Humans
  • Incidence
  • Male
  • Mutation
  • Prevalence
  • Receptors, Drug / genetics*
  • Sodium Chloride Symporters / genetics*
  • Solute Carrier Family 12, Member 3
  • Symporters / genetics*


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