title: Genetic variation, C-reactive protein levels, and incidence of diabetes.
abstract: C-reactive protein (CRP) has been shown to be associated with type 2 diabetes, but whether CRP has a causal role is not yet clear. We examined the association in the Rotterdam Study, a population-based prospective cohort study. The association of baseline serum CRP and incident diabetes during follow-up was investigated, and a meta-analysis was conducted on the BMI-adjusted relation of CRP and diabetes. Furthermore, the association of CRP haplotypes with serum CRP and risk of diabetes was assessed. The age- and sex-adjusted hazard ratio for diabetes was 1.41 (95% CI 1.29-1.54) per 1 SD increase in natural logarithm of CRP, and it was 1.88, 2.16, and 2.83 for the second, third, and fourth quartiles of CRP, respectively, compared with the first quartile. The risk estimates attenuated but remained statistically significant after additional adjustment for obesity indexes, which agreed with the results of the meta-analysis. The most common genetic haplotype was associated with a significantly lower CRP level compared with the three other haplotypes. The risk of diabetes was significantly higher in the haplotype with the highest serum CRP level compared with the most common haplotype (OR 1.45, 95% CI 1.08-1.96). These findings support the hypothesis that serum CRP enhances the development of diabetes.
authors.affiliation: Department of Epidemiology and Biostatistics, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: Isabella
authors.initials: I
authors.lastname: Kardys
authors.forename: Moniek P M
authors.initials: MP
authors.lastname: de Maat
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: Aart H
authors.initials: AH
authors.lastname: Bootsma
authors.forename: Theo
authors.initials: T
authors.lastname: Stijnen
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Miranda T
authors.initials: MT
authors.lastname: Schram
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
mesh_terms: D000368:Aged; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D002097:C-Reactive Protein