| Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke. | |
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MedLine Citation:
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PMID: 21430556 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jonas Dahlberg; Gustav Smith; Bo Norrving; Peter Nilsson; Bo Hedblad; Gunnar Engström; Håkan Lövkvist; Joyce Carlson; Arne Lindgren; Olle Melander |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hypertension Volume: 29 ISSN: 1473-5598 ISO Abbreviation: J. Hypertens. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-08 Completed Date: 2011-07-29 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 884-9 Citation Subset: IM |
Copyright Information:
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© 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins |
Affiliation:
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Clinical Research Center (CRC), Entrance 72, Bldg 91, Floor 12, Malmö University Hospital, SE 205 02 Malmö, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Aged, 80 and over Brain Ischemia / genetics* Case-Control Studies Epithelial Sodium Channel / physiology* Female Humans Immediate-Early Proteins / genetics*, physiology Logistic Models Male Middle Aged Protein-Serine-Threonine Kinases / genetics*, physiology Stroke / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Epithelial Sodium Channel; 0/Immediate-Early Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/serum-glucocorticoid regulated kinase |
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