title: Circulating beta-carotene levels and type 2 diabetes-cause or effect?
abstract: OBJECTIVE
  Circulating beta-carotene levels are inversely associated with risk of type 2 diabetes, but the causal direction of this association is not certain. In this study we used a Mendelian randomisation approach to provide evidence for or against the causal role of the antioxidant vitamin beta-carotene in type 2 diabetes.
  
  
  METHODS
  We used a common polymorphism (rs6564851) near the BCMO1 gene, which is strongly associated with circulating beta-carotene levels (p = 2 x 10(-24)), with each G allele associated with a 0.27 standard deviation increase in levels. We used data from the InCHIANTI and Uppsala Longitudinal Study of Adult Men (ULSAM) studies to estimate the association between beta-carotene levels and type 2 diabetes. We next used a triangulation approach to estimate the expected effect of rs6564851 on type 2 diabetes risk and compared this with the observed effect using data from 4549 type 2 diabetes patients and 5579 controls from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium.
  
  
  RESULTS
  A 0.27 standard deviation increase in beta-carotene levels was associated with an OR of 0.90 (95% CI 0.86-0.95) for type 2 diabetes in the InCHIANTI study. This association was similar to that of the ULSAM study (OR 0.90 [0.84-0.97]). In contrast, there was no association between rs6564851 and type 2 diabetes (OR 0.98 [0.93-1.04], p = 0.58); this effect size was also smaller than that expected, given the known associations between rs6564851 and beta-carotene levels, and the associations between beta-carotene levels and type 2 diabetes.
  
  
  CONCLUSIONS
  Our findings in this Mendelian randomisation study are in keeping with randomised controlled trials suggesting that beta-carotene is not causally protective against type 2 diabetes.
authors: Peninsula Medical School, Exeter, UK.
authors: J R B
authors: JR
authors: Perry
authors: L
authors: L
authors: Ferrucci
authors: S
authors: S
authors: Bandinelli
authors: J
authors: J
authors: Guralnik
authors: R D
authors: RD
authors: Semba
authors: N
authors: N
authors: Rice
authors: D
authors: D
authors: Melzer
authors: R
authors: R
authors: Saxena
authors: L J
authors: LJ
authors: Scott
authors: M I
authors: MI
authors: McCarthy
authors: A T
authors: AT
authors: Hattersley
authors: E
authors: E
authors: Zeggini
authors: M N
authors: MN
authors: Weedon
authors: T M
authors: TM
authors: Frayling
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics
chemical_list: D019207:beta Carotene; C493358:BCO1 protein, human; D050559:beta-Carotene 15,15'-Monooxygenase