title: Common variants in epithelial sodium channel genes contribute to salt sensitivity of blood pressure: The GenSalt study.
abstract: BACKGROUND
  Rare mutations of the epithelial sodium channel (ENaC) lead to mendelian forms of salt-sensitive hypertension or salt-wasting hypotension. We aimed to examine the association between common variants in the ENaC genes and salt sensitivity of blood pressure (BP).
  
  
  RESULTS
  A total of 1906 Han Chinese participated in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, which includes a 7-day low-sodium intake (51.3 mmol sodium/d) followed by a 7-day high-sodium intake (307.8 mmol sodium/d). Nine BP measurements were obtained at baseline and each intervention period using a random-zero sphygmomanometer. Single-nucleotide polymorphisms, both tagging and functional, from the 3 ENaC subunits, α, β, and γ (SCNN1A, SCNN1B, and SCNN1G), were genotyped. Multiple common single-nucleotide polymorphisms in SCNN1G were significantly associated with BP response to low-sodium intervention (rs4073930, P=1.7×10(-5); rs4073291, P=1.1×10(-5); rs7404408, P=1.9×10(-5); rs5735, P=3.0×10(-4); rs4299163, P=0.004; and rs4499238, P=0.002) even after correcting for multiple testing. For example, under an additive model, the minor allele G of SNP rs4073291 was associated with 1.33 mm Hg lower systolic BP reduction during low-sodium intervention.
  
  
  CONCLUSIONS
  This large dietary sodium intervention study indicates that common variants of ENaC subunits may contribute to the variation of BP response to dietary sodium intake. Future studies are warranted to confirm these findings in an independent population and to identify functional variants for salt sensitivity.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00721721.
authors.affiliation: Department of Epidemiology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.forename: Cashell E
authors.initials: CE
authors.lastname: Jaquish
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
authors.forename: Fanghong
authors.initials: F
authors.lastname: Lu
authors.forename: Jixiang
authors.initials: J
authors.lastname: Ma
authors.forename: Jianjun
authors.initials: J
authors.lastname: Mu
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Mei
authors.forename: L Lee
authors.initials: LL
authors.lastname: Hamm
authors.forename: Jiang
authors.initials: J
authors.lastname: He
mesh_terms: D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects*; D053503:Epithelial Sodium Channels / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007022:Hypotension / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics; D012492:Salts / Q000494:pharmacology; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D053503:Epithelial Sodium Channels; D021122:Protein Subunits; D012492:Salts; D012982:Sodium, Dietary