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Jonas Dahlberg

Physician

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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.

Author

  • Jonas Dahlberg
  • Gustav Smith
  • Bo Norrving
  • Peter Nilsson
  • Bo Hedblad
  • Gunnar Engström
  • Håkan Lövkvist
  • Joyce Carlson
  • Arne Lindgren
  • Olle Melander

Summary, in English

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.

Department/s

  • Cardiovascular Research - Hypertension
  • Neurology, Lund
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Epidemiology
  • Division of Clinical Chemistry and Pharmacology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2011

Language

English

Pages

884-889

Publication/Series

Journal of Hypertension

Volume

29

Document type

Journal article

Publisher

Lippincott Williams & Wilkins

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1473-5598