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A non-conservative polymorphism in the IL-6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population.

Journal article
Authors Anna Benrick
Pernilla Jirholt
Ingrid Wernstedt
Maria Gustafsson
Juergen Scheller
Anna-Lena Eriksson
Jan Borén
Thomas Hedner
Claes Ohlsson
Torleif Härd
Stefan Rose-John
John-Olov Jansson
Published in Regulatory peptides
Volume 146
Issue 1-3
Pages 189-96
ISSN 0167-0115
Publication year 2008
Published at Wallenberg Laboratory
Institute of Neuroscience and Physiology, Department of Physiology
Institute of Medicine, Department of Clinical Trials and Entrepreneurship
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Medicine, Department of Internal Medicine
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 189-96
Language en
Links dx.doi.org/10.1016/j.regpep.2007.09...
Keywords Adult, Aged, Cells, Cultured, Comorbidity, Cytokine Receptor gp130, genetics, Female, Humans, Hypertension, epidemiology, genetics, Interleukin-6, genetics, Male, Middle Aged, Myocardial Infarction, epidemiology, genetics, Polymorphism, Genetic, Variation (Genetics)
Subject categories Medical and Health Sciences

Abstract

Inflammation is a key component in the development of atherosclerosis, and myocardial infarction (MI); therefore we investigated the association between an interleukin-6 signal transducer (IL6ST)/gp130 polymorphism, gp130 function and risk of MI. Structural modeling suggested that a non-conservative single nucleotide polymorphism in the gp130, Gly148Arg, can change the stability and functional properties of the molecule. In vitro studies were done with BAF/3 cells lacking endogenous gp130. Cells stably transfected with the gp130 148Arg variant proliferated less and showed slightly lower STAT-3 phosphorylation in response to gp130 stimulation as compared to cells transfected with gp130 148Gly. In a prospectively followed hypertensive cohort we identified 167 patients who suffered a MI during the study and compared them to matched controls (mean age 57 years, 73% males, n=482). Carriers of the 148Arg variant (f(Arg)=0.12) of the gp130 receptor had decreased odds ratio for MI in univariate analysis (0.56, 95% CI 0.34-0.91, p=0.02). In conclusion, a genetically determined structural variant of the IL-6 receptor subunit gp130 is, independently of other known risk factors, associated with decreased risk of MI. The variant is also associated with decreased IL-6 responsiveness and could lead to a configuration change in the gp130 receptor.

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