An RBP4 promoter polymorphism increases risk of type 2 diabetes.
OBJECTIVE
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 1alpha 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
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.
van Hoek
M
M
Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
Dehghan
A
A
Zillikens
M C
MC
Hofman
A
A
Witteman
J C
JC
Sijbrands
E J G
EJ
D000368:Aged; D001794:Blood Pressure; D015992:Body Mass Index; D049628:Body Size; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005838:Genotype; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D009426:Netherlands; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics*; D012307:Risk Factors
D051538:Hepatocyte Nuclear Factor 1-alpha; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma