title: No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.
abstract: Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
authors.affiliation: Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK. robert.scott@mrc-epid.cam.ac.uk
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mesh_terms: D001786:Blood Glucose / Q000235:genetics* / Q000378:metabolism*; D015992:Body Mass Index; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D005838:Genotype; D006801:Humans; D008019:Life Style; D009043:Motor Activity / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D001786:Blood Glucose