title: Impact of alphaENaC polymorphisms on the risk of ischemic cerebrovascular events: a multicenter case-control study.
abstract: BACKGROUND
  Amiloride-sensitive epithelial sodium channels (ENaCs) are important candidates in the development of hypertension, which is a major risk factor for stroke. Two single-nucleotide polymorphisms (SNPs) in the gene that encodes the ENac alpha-subunit (alphaENaC) have been identified. We evaluated those SNPs for a possible association with ischemic cerebrovascular events (ICEs).
  
  
  RESULTS
  We genotyped 1399 patients with ICEs [median age, 70 years; interquartile range, 58-78 years; 745 (53%) men] and 1076 control individuals without vascular disease [47 (39-58) years; 557 (52%) men] for the SNPs Trp493Arg and Ala663Thr. The SNP frequencies at nucleotide 3977 (Trp493Arg) in the alphaENaC gene were significantly different in patients and controls. Carriers of 493Arg had a 1.78-fold increased risk (95% confidence interval, 1.02-3.12) for ICEs compared with Trp/Trp carriers. Interaction analysis revealed that the relative risk was even higher in women in the lowest age tertile [adjusted odds ratio, 3.26 (1.10-9.72)].
  
  
  CONCLUSIONS
  Carriers of the 493Arg allele are at increased risk for ICEs compared with Trp/Trp carriers. The effect is independent of traditional vascular risk factors and is particularly evident in younger women. The Trp493Arg variant in alphaENaC may represent an important candidate genetic susceptibility factor in the development of ICEs.
authors.affiliation: Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria.
authors.forename: Kety
authors.initials: K
authors.lastname: Hsieh
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lalouschek
authors.forename: Martin
authors.initials: M
authors.lastname: Schillinger
authors.forename: Georg
authors.initials: G
authors.lastname: Endler
authors.forename: Manuela
authors.initials: M
authors.lastname: Reisinger
authors.forename: Michael
authors.initials: M
authors.lastname: Janisiw
authors.forename: Wilfried
authors.initials: W
authors.lastname: Lang
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cheng
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D053503:Epithelial Sodium Channels; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D015222:Sodium Channels / Q000235:genetics*; D020521:Stroke / Q000235:genetics
chemical_list: D053503:Epithelial Sodium Channels; D021122:Protein Subunits; D015222:Sodium Channels