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DOI: 10.1055/s-0030-1249637
© Georg Thieme Verlag KG Stuttgart · New York
Glucokinase-activating GCKR Polymorphisms Increase Plasma Levels of Triglycerides and Free Fatty Acids, but do not Elevate Cardiovascular Risk in the Ludwigshafen Risk and Cardiovascular Health Study
Publikationsverlauf
received 05.11.2009
accepted 24.02.2010
Publikationsdatum:
29. März 2010 (online)

Abstract
Two strongly correlated polymorphisms located within the gene of the glucokinase regulator protein (GKRP), rs780094 and rs1260326, are associated with increased plasma triglyceride levels and provide a genetic model for the long-term activation of hepatic glucokinase. Because pharmacological glucokinase activators are evaluated for the treatment of diabetes, the aim of the study was to assess if these polymorphisms could provide evidence for an increased cardiovascular risk of long-term glucokinase activation. Therefore, these polymorphisms were tested in 3 500 patients of the Ludwigshafen Risk and Cardiovascular Health study, which was designed to assess cardiovascular risk factors. The two variants were associated with a significant increase of both plasma triglycerides (p<0.0001) and VLDL triglyceride levels (p<0.0001). Plasma free fatty acid concentrations were also significantly elevated (p<0.0078). LDL and HDL cholesterol levels were unchanged. No association was found with respect to coronary stenosis, myocardial infarction, left ventricular wall hypertrophy, and hypertension. In conclusion, long-term genetic glucokinase activation by the GKRP polymorphisms was not associated with an increased cardiovascular risk in the study population.
Key words
common polymorphism - glucokinase - metabolic syndrome - type 2 diabetes - cardiovascular disease
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1 These authors contributed equally to the work.
Correspondence
D. Schmoll
Sanofi-Aventis
R & D
Industriepark H825
65926 Frankfurt
Germany
Telefon: +49/69/30516642
Fax: +49/69/30581901
eMail: dieter.schmoll@sanofi-aventis.com