Authors: M van Hoek A Dehghan M C Zillikens A Hofman J C Witteman E J G Sijbrands
Publish Date: 2008/05/22
Volume: 51, Issue: 8, Pages: 1423-
Abstract
Retinolbinding protein 4 RBP4 originally known for retinol transport was recently identified as an adipokine affecting insulin resistance The RBP4 −803GA promoter polymorphism influences binding of hepatic nuclear factor 1α and is associated with type 2 diabetes in case–control studies We hypothesised that the RBP4 −803GA polymorphism increases type 2 diabetes risk at a populationbased level In addition information on retinol intake and plasma vitamin A levels enabled us to explore the possible underlying mechanismIn the Rotterdam Study a prospective populationbased followup study the −803GA polymorphism was genotyped In Cox proportional hazards models associations of the −803GA polymorphism and retinol intake with type 2 diabetes risk were examined Moreover the interaction of the polymorphism with retinol intake on type 2 diabetes risk was assessed In a subgroup of participants the association of the polymorphism and vitamin A plasma levels was investigatedHomozygous carriers of the −803A allele had increased risk of type 2 diabetes HR 183 95 CI 126–266 Retinol intake was not associated with type 2 diabetes risk and showed no interaction with the RBP4 −803GA polymorphism Furthermore there was no significant association of the polymorphism with plasma vitamin A levelsOur results provide evidence that homozygosity for the RBP4 −803A allele is associated with increased risk of type 2 diabetes in the Rotterdam population This relationship was not clearly explained by retinol intake and vitamin A plasma levels Therefore we cannot differentiate between a retinoldependent or independent mechanism of this RBP4 variant
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