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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Dahlberg, JonasLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups (author)

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

Article/chapterEnglish2011

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2011

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LIBRIS-ID:oai:lup.lub.lu.se:1ca257bd-a640-4fc2-8e9a-553215764957
https://lup.lub.lu.se/record/1883532URI
https://doi.org/10.1097/HJH.0b013e3283455117DOI

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Language:English
Summary in:English

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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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Smith, GustavLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)med-gvs (author)
Norrving, BoLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)neur-bno (author)
Nilsson, PeterLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups(Swepub:lu)medf-pni (author)
Hedblad, BoLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups(Swepub:lu)medf-bhe (author)
Engström, GunnarLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups(Swepub:lu)smi-gen (author)
Lövkvist, HåkanLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-hlk (author)
Carlson, JoyceLund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)klke-jca (author)
Lindgren, ArneLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)neur-ali (author)
Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
Kardiovaskulär forskning - hypertoniForskargrupper vid Lunds universitet (creator_code:org_t)

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In:Journal of Hypertension29, s. 884-8891473-5598

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By the author/editor: Dahlberg, Jonas; Smith, Gustav; Norrving, Bo; Nilsson, Peter; Hedblad, Bo; Engström, Gunnar; show more...; Lövkvist, Håkan; Carlson, Joyce; Lindgren, Arne; Melander, Olle; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

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