title: A two-step association study identifies CAV2 rs2270188 single nucleotide polymorphism interaction with fat intake in type 2 diabetes risk.
abstract: Multiple genetic and environmental factors underlie the etiology of type 2 diabetes. To evaluate the influence of the relationship between dietary fat intake and single nucleotide polymorphisms (SNPs) in genes involved in fat assimilation on disease susceptibility, a 2-step approach using an exploratory case-control study (n = 192/384) and an independent, confirmatory case-cohort study (n = 614/2248) taken from the same prospective study population (European Prospective Investigation into Cancer and Nutrition-Potsdam) was used. Sixty-three SNPs in 32 genes were initially analyzed. Total intake of fat and fatty acid intake were calculated from validated baseline FFQ. The SNP × nutrient interaction was tested in multivariate adjusted regression models. The initial screening step revealed evidence that, for 4 SNPs (CAV2 rs2270188, DBI rs2084202, PPARG rs1801282, and SREBF1 rs2297508), disease susceptibility might depend on the amount and quality of fat intake. The insulin receptor regulator CAV2 rs2270188 G > T SNP was found to interact with dietary fat in the confirmatory case-cohort study. Using pooled data, homozygous individuals of the rare T-allele showed a 100% greater risk of type 2 diabetes if daily fat intake was increased from 30 to 40 % energy. An increase in dietary SFA from 10 to 20 % energy predicted an ~200% greater risk of type 2 diabetes. We found preliminary evidence that CAV2 rs2270188 interacts with dietary fat to affect risk of type 2 diabetes.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D051243:Caveolin 2 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054647:Nutrigenomics; D009747:Nutritional Physiological Phenomena / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D011795:Surveys and Questionnaires
chemical_list: D051243:Caveolin 2; D004041:Dietary Fats; D047495:PPAR gamma; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1