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Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke.

Dahlberg, Jonas LU ; Smith, Gustav LU ; Norrving, Bo LU ; Nilsson, Peter LU ; Hedblad, Bo LU ; Engström, Gunnar LU ; Lövkvist, Håkan LU ; Carlson, Joyce LU ; Lindgren, Arne LU and Melander, Olle LU (2011) In Journal of Hypertension 29. p.884-889
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... (More)
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. CONCLUSION: 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Hypertension
volume
29
pages
884 - 889
publisher
Lippincott Williams & Wilkins
external identifiers
  • WOS:000289276600012
  • PMID:21430556
  • Scopus:79954843186
ISSN
1473-5598
DOI
10.1097/HJH.0b013e3283455117
language
English
LU publication?
yes
id
1ca257bd-a640-4fc2-8e9a-553215764957 (old id 1883532)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21430556?dopt=Abstract
date added to LUP
2011-04-01 20:49:30
date last changed
2016-12-04 04:38:34
@misc{1ca257bd-a640-4fc2-8e9a-553215764957,
  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 &lt; 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. CONCLUSION: 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.},
  author       = {Dahlberg, Jonas and Smith, Gustav and Norrving, Bo and Nilsson, Peter and Hedblad, Bo and Engström, Gunnar and Lövkvist, Håkan and Carlson, Joyce and Lindgren, Arne and Melander, Olle},
  issn         = {1473-5598},
  language     = {eng},
  pages        = {884--889},
  publisher    = {ARRAY(0xe2ffb98)},
  series       = {Journal of Hypertension},
  title        = {Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke.},
  url          = {http://dx.doi.org/10.1097/HJH.0b013e3283455117},
  volume       = {29},
  year         = {2011},
}