Impact of alphaENaC polymorphisms on the risk of ischemic cerebrovascular events: a multicenter case-control study.
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.
Hsieh
Kety
K
Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria.
Lalouschek
Wolfgang
W
Schillinger
Martin
M
Endler
Georg
G
Reisinger
Manuela
M
Janisiw
Michael
M
Lang
Wilfried
W
Cheng
Suzanne
S
Wagner
Oswald
O
Mannhalter
Christine
C
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
D053503:Epithelial Sodium Channels; D021122:Protein Subunits; D015222:Sodium Channels