KCNK17 genetic variants in ischemic stroke.
BACKGROUND
Genetic factors contribute to the development of ischemic stroke (IS). In order to identify susceptibility variants, we analyzed single nucleotide polymorphisms (SNPs) that had been previously linked to stroke in a genome-wide association study.


METHODS
We analyzed 12 SNPs in a White population comprising IS patients and healthy controls. The analysis was adjusted for confounding variables and stratified by stroke etiology. Functional studies were then performed to elucidate the role of these variants in IS.


RESULTS
In a preliminary analysis of 268 controls and 531 IS cases, the rs10947803 SNP of KCNK17 (p=0.012) and the rs7506045 of IMPA2 (p=0.040) were associated with IS, although only the KCNK17 gene was an independent risk factor for IS. In a second phase, analysis of 271 new IS cases revealed that the A allele of rs10947803 was associated with stroke after correction for Bonferroni (OR=1.48; 95% CI, 1.14-1.91, p=0.003). Gene expression analysis revealed that KCNK17 mRNA levels were higher in the IS cases in the acute phase than in controls (14+/-78% vs. 91+/-41, p=0.002) but not in the chronic phase (56+/-57%; p=0.230). Moreover, RNA levels depended on the alleles of the rs10947803 SNP in the control group (p=0.021) and in the chronic phase (p=0.033).


CONCLUSIONS
The A allele of the rs10947803 variant of KCNK17 was associated with increased risk of IS and increased levels of KCNK17 gene expression. The role of this potassium channel gene in IS opens diagnostic and therapeutic expectations and merits further investigation.
Domingues-Montanari
Sophie
S
Neurovascular Research Laboratory and Neurovascular Unit, Neurology and Medicine Departments-Universitat Autònoma de Barcelona, Vall d'Hebron Hospital, Passeig Vall d'Hebron 119-129, Barcelona, Spain.
Fernández-Cadenas
Israel
I
Del Río-Espinola
Alberto
A
Mendioroz
Maite
M
Fernandez-Morales
Jessica
J
Corbeto
Natalia
N
Delgado
Pilar
P
Ribó
Marc
M
Rubiera
Marta
M
Obach
Victor
V
Martí-Fàbregas
Joan
J
Freijo
Marimar
M
Serena
Joaquin
J
Montaner
Joan
J
D000368:Aged; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics*; D020521:Stroke / Q000235:genetics*
C423407:KCNK17 protein, human; D024683:Potassium Channels, Tandem Pore Domain