Hamostaseologie 2011; 31(03): 196-200
DOI: 10.5482/ha-1142
Original article
Schattauer GmbH

Evaluation of the PC-1 K121Q and G2906C variants as independent risk factors for ischaemic stroke

Evaluierung der Varianten PC-1-K121Q und G2906C als unabhängige Risikofaktoren für Schlaganfall
M. Rieger
1   Department of Laboratory Medicine, Medical University of Vienna, Austria
,
G. Endler
1   Department of Laboratory Medicine, Medical University of Vienna, Austria
,
M. Funk
1   Department of Laboratory Medicine, Medical University of Vienna, Austria
,
W. Lalouschek
2   Department of Clinical Neurology, Medical University of Vienna, Austria
,
W. Lang
3   Hospital Barmherzige Brüder, Vienna, Austria
,
C. Mannhalter
1   Department of Laboratory Medicine, Medical University of Vienna, Austria
,
R. Sunder-Plassmann
1   Department of Laboratory Medicine, Medical University of Vienna, Austria
› Author Affiliations
This study was supported by grant number 9996 from the Jubiläumsfonds der Österreichischen Nationalbank and grant number P16563-B13 from the Austrian Science Foundation.
Further Information

Publication History

received: 16 August 2010

accepted in revised form: 27 May 2011

Publication Date:
28 December 2017 (online)

Summary

Overexpression of plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor tyrosine kinase activity and thus favours insulin resistance and atherosclerotic vascular disease. Recent findings indicate that the minor variant K121Q in the PC-1 gene confers an increased risk for early myocardial infarction independent of other established risk factors. We hypothesized that genetic variants in PC-1 may also influence the risk for cerebrovascular disease.

Aim

Therefore, we assessed the association of the PC-1 K121Q variant in the coding region and a polymorphism (G2906C) in the 3’ untranslated region of the PC-1 gene with the risk of stroke.

Patients

We analyzed 1014 patients with a history of ischaemic stroke from the Vienna stroke registry and 1001 control individuals without vascular disease.

Results, conclusion

Genotype frequencies of both genetic variants were similar in patients and controls in the total study population. By multivariate analysis, no interactions were observed between the PC-1 genotype and established vascular risk factors. However, the PC-1 2906C allele was significantly more frequent in patients who suffered from stroke before the age of 40 years. In these patients the risk for ischaemic stroke was increased fourfold.

Zusammenfassung

Vermehrte Expression von Plasma-Zellmembrane-Glykoprotein-1 (PC-1) hemmt die Tyrosinkinase-Aktivität des Insulinrezeptors und begünstigt dadurch die Entstehung von Insulinresistenz und atherosklerotischen Gefäßerkrankungen. Vor kurzem wurde gezeigt, dass die untergeordnete Variante K121Q im PC-1-Gen – unabhängig von anderen etablierten Risikofaktoren – ein erhöhtes Risiko für frühzeitigen Myokardinfarkt bewirkt.

Ziel

Wir vermuteten, dass genetische Varianten in PC-1 auch das Risiko für zerebrovaskuläre Erkrankungen beeinflussen könnten.

Patienten

Wir untersuchten die Assoziation der PC-1-K121Q-Variante in der kodierenden Region und die Rolle des Polymorphismus (G2906C) in der 3’-untranslatierten Region des PC-1-Gens mit dem Schlaganfallrisiko bei 1014 Patienten mit Vorgeschichte eines ischämischen Insults des Wiener Schlaganfall-Registers sowie bei 1001 Kontrollindividuen ohne vaskuläre Erkrankungen.

Ergebnisse, Schlussfolgerungen

Die Genotypfrequenzen beider Polymorphismen waren bei Patienten und Kontrollpersonen bezogen auf die gesamte Studienpopulation vergleichbar. Multivarianzanalysen zeigten keine Interaktionen zwischen PC-1-Genotyp und etablierten vaskulären Risikofaktoren. Allerdings beobachteten wir ein signifikant häufigeres Auftreten des 2906C-Allels bei Patienten, die bereits vor dem 40. Lebensjahr einen Schlaganfall erlitten hatten, verbunden mit einem vierfach erhöhten Schlaganfallrisiko.

 
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