title: Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke.
abstract: OBJECTIVE
  Serum and glucocorticoid regulated kinase 1 (SGK1) expression is increased by aldosterone and is a key regulator of the amiloride-sensitive sodium channel (ENaC) in the distal nephron. We have previously shown that two SNPs in SGK1 (rs1057293 and rs1743966) are associated with blood pressure variation and blood pressure progression in the general population. Therefore, we tested the association of these variants with ischaemic stroke.
  
  
  METHODS
  Using logistic regression, we analysed rs1057293 and rs1743966 for association with ischaemic stroke in two independent age-matched and sex-matched case-control groups from the twin cities of Lund (cases n=1837 and controls n=947) and Malmö (cases n=888 and controls n=893) in the Scania region of southern Sweden.
  
  
  RESULTS
  In additive models adjusted for hypertension, smoking and diabetes, the major allele (G) of rs1057293 was associated (odds ratio, 95% confidence interval; P value) with ischaemic stroke with similar effect size in both studies; in Lund (1.35, 1.11-1.64; P=0.002) and Malmö (1.30, 1.03-1.65; P=0.027). When the two studies were pooled, the overall association was 1.32, 1.14-1.52; P<0.001. The major allele of rs1743966 (A), which was in linkage disequilibrium with rs1057293, showed a similar trend as rs1057293 G-allele but with slightly weaker effect size and P value.
  
  
  CONCLUSIONS
  In two independent but ethnically similar populations, we observed an association between genetic variants in SGK1 and ischaemic stroke. Interestingly, the association seems to be at least partially independent of blood pressure. This could imply that cerebrovascular ENaC or other SGK1-regulated proteins may be of importance for development of ischaemic stroke.
authors: Clinical Research Center (CRC), Entrance 72, Bldg 91, Floor 12, Malmö University Hospital, SE 205 02 Malmö, Sweden.
authors: Jonas
authors: J
authors: Dahlberg
authors: Gustav
authors: G
authors: Smith
authors: Bo
authors: B
authors: Norrving
authors: Peter
authors: P
authors: Nilsson
authors: Bo
authors: B
authors: Hedblad
authors: Gunnar
authors: G
authors: Engström
authors: Håkan
authors: H
authors: Lövkvist
authors: Joyce
authors: J
authors: Carlson
authors: Arne
authors: A
authors: Lindgren
authors: Olle
authors: O
authors: Melander
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D053503:Epithelial Sodium Channels / Q000502:physiology*; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000502:physiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D020521:Stroke / Q000235:genetics*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases