title: Body mass index and C-174G interleukin-6 promoter polymorphism interact in predicting type 2 diabetes.
abstract: Increased levels of IL-6 add further risk to the impact of obesity in respect to the development of type 2 diabetes mellitus (T2DM). A C-174G polymorphism within the IL-6 promoter region was shown to influence transcription rate of IL-6. We made use of a nested case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort of 27,548 individuals, selecting 188 T2DM cases and 376 controls to investigate this polymorphism in respect to development of T2DM. This polymorphism was found to modify the correlation between body mass index (BMI) and IL-6 by showing a much stronger increase of IL-6 at increased BMI for CC genotypes compared with GG genotypes. Interestingly, C-174G polymorphism was found to be an effect modifier for the impact of BMI regarding T2DM. Whereas BMI greater than or equal to 28 kg/m(2) increased the risk of T2DM 3.44-fold [95% confidence interval (CI), 1.34- to 8.24-fold] for GG genotypes and 2.94-fold (95% CI, 1.56- to 5.56-fold) for GC genotypes, we found a 17.68-fold (95% CI, 3.57- to 87.66-fold) increase in risk for CC genotypes. In conclusion, obese individuals with BMI greater than or equal to 28 kg/m(2) carrying the CC genotype showed a more than 5-fold increased risk of developing T2DM compared with the remaining genotypes and, hence, might profit most from weight reduction.
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany. mmoehlig@mail.dife.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Möhlig
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Martin
authors.initials: M
authors.lastname: Osterhoff
authors.forename: Anja
authors.initials: A
authors.lastname: Kroke
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Manuela M
authors.initials: MM
authors.lastname: Bergmann
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
authors.forename: Kurt
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
mesh_terms: D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D003596:Cytosine; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006147:Guanine; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D006147:Guanine; D003596:Cytosine