title: High-frequency variant p.T60M in NaCl cotransporter and blood pressure variability in Han Chinese.
abstract: OBJECTIVE
  Frequent studies have confirmed that homozygous or compound heterozygous loss-of-function mutation p.Thr60Met in NaCl cotransporter (NCC) lead to the salt-wasting Gitelman's syndrome (GS) of hypotension. The finding that Thr60 is a key SPAK/OSR1 phosphorylation site on NCC also raises the possible importance of Thr60 in regulating the activity of NCC and blood pressure (BP). However, the association of heterozygous NCC mutation p.Thr60Met and BP has not yet been studied.
  
  
  METHODS
  We collected 38 heterozygous mutation p.Thr60Met carriers, respectively, from 14 GS families confirmed by our previous studies and 1,000 unrelated Han Chinese, and matched them pairwise (sex, age ±2 years and BMI ±1) with 38 unrelated healthy controls. BP and biochemistry data were obtained. Student's t test and χ(2) test were used to compare the differences between these study subjects with the heterozygous variant p.T60M and the controls. p < 0.05 was considered statistically significant.
  
  
  RESULTS
  p.Thr60Met carriers had markedly lower BP (systolic 110.3 ± 13.5 vs. 119.1 ± 15.0 mm Hg; diastolic 70.2 ± 7.0 vs. 75.4 ± 8.2 mm Hg, p < 0.01) than controls. p.Thr60Met heterozygotes had higher fasting plasma glucose concentration (5.35 ± 0.73 vs. 4.95 ± 0.69 mmol/l, p < 0.01). 14 carriers versus 6 control subjects had impaired fasting glucose (36.8 vs. 15.8%, p < 0.01), and p.Thr60Met carriers had higher 24-hour urinary sodium excretion than controls but not significantly (170.2 ± 35.6 vs. 159.5 ± 39.0 mmol, p = 0.10).
  
  
  CONCLUSIONS
  The NCC mutation p.Thr60Met carriers in Han populations have markedly lower BP and slightly higher fasting plasma glucose compared with normal controls.
authors.affiliation: Department of Nephrology, Affiliated Hospital of Qingdao University School of Medicine, Qingdao, PR China. lepingshao@163.com
authors.forename: Leping
authors.initials: L
authors.lastname: Shao
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Lang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Haitao
authors.initials: H
authors.lastname: Niu
authors.forename: Shiguo
authors.initials: S
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D005215:Fasting; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012964:Sodium / Q000652:urine; D049992:Sodium Chloride Symporters / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D049992:Sodium Chloride Symporters; D012964:Sodium