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

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.

• 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
• Journal: Regulatory peptides (Regul Pept) Vol. 146 Issue 1-3 Pg. 189-96 (Feb 07 2008) ISSN: 0167-0115 [Print] Netherlands
• PMID: 17997171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Cytokine Receptor gp130

Topics

• Adult
• Aged
• Cells, Cultured
• Comorbidity
• Cytokine Receptor gp130 (genetics)
• Female
• Genetic Variation
• Humans
• Hypertension (epidemiology, genetics)
• Interleukin-6 (genetics)
• Male
• Middle Aged
• Myocardial Infarction (epidemiology, genetics)
• Polymorphism, Genetic