An RBP4 promoter polymorphism increases risk of type 2 diabetes

M van der Hoek, Abbas Dehghan, M.C. Zillikens, Bert Hofman, JCM Witteman, E.J.G. Sijbrands

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Abstract

Aims/hypothesis Retinol-binding 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 la 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 population-based level. In addition, information on retinol intake and plasma vitamin A levels enabled us to explore the possible underlying mechanism. Methods In the Rotterdam Study, a prospective, population-based, follow-up 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 investigated. Results Homozygous carriers of the -803A allele had increased risk of type 2 diabetes (HR 1.83; 95% CI 1.26-2.66). 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 levels. Conclusions/interpretation Our 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 retinol-dependent or -independent mechanism of this RBP4 variant.
Original languageUndefined/Unknown
Pages (from-to)1423-1428
Number of pages6
JournalDiabetologia
Volume51
Issue number8
DOIs
Publication statusPublished - 2008

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