title: Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study.
abstract: Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). In this study, we determined whether polymorphisms in these genes modified the effect of changes in physical activity (PA) on the risk of T2D in the DPS. Moreover, we assessed whether the polymorphisms modified the effect of changes in PA on changes in measures of body fat, serum lipids, and blood pressure during the first year of the follow-up of the DPS. Overweight subjects with IGT (n = 487) were followed for an average of 4.1 years, and PA was assessed annually with a questionnaire. The interactions of the polymorphisms with changes in total and moderate-to-vigorous PA on the conversion to T2D during the 4.1-year follow-up were assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). Univariate analysis of variance was used to assess interactions on changes in continuous variables during the first year of the follow-up. No interaction between the polymorphisms and PA on the conversion to T2D was found. The Leu72Met (rs696217) polymorphism in GHRL modified the effect of moderate-to-vigorous PA on changes in weight and waist circumference, the -501A/C (rs26802) polymorphism in GHRL modified the effect of total and moderate-to-vigorous PA on change in high-density lipoprotein cholesterol, and the Lys109Arg (rs1137100) polymorphism in LEPR modified the effect of total PA on change in blood pressure. In conclusion, genetic variation may modify the magnitude of the beneficial effects of PA on characteristics of the metabolic syndrome in persons with IGT.
authors.affiliation: Institute of Biomedicine, Physiology, University of Kuopio, Kuopio 70211, Finland. tuomas.kilpelainen@uku.fi
authors.forename: Tuomas O
authors.initials: TO
authors.lastname: Kilpeläinen
authors.forename: Timo A
authors.initials: TA
authors.lastname: Lakka
authors.forename: David E
authors.initials: DE
authors.lastname: Laaksonen
authors.forename: Ursula
authors.initials: U
authors.lastname: Mager
authors.forename: Titta
authors.initials: T
authors.lastname: Salopuro
authors.forename: Agata
authors.initials: A
authors.lastname: Kubaszek
authors.forename: Boryana
authors.initials: B
authors.lastname: Todorova
authors.forename: Olli
authors.initials: O
authors.lastname: Laukkanen
authors.forename: Jaana
authors.initials: J
authors.lastname: Lindström
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.forename: Helena
authors.initials: H
authors.lastname: Hämäläinen
authors.forename: Sirkka
authors.initials: S
authors.lastname: Aunola
authors.forename: Pirjo
authors.initials: P
authors.lastname: Ilanne-Parikka
authors.forename: Sirkka
authors.initials: S
authors.lastname: Keinänen-Kiukaanniemi
authors.forename: Jaako
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
mesh_terms: D000886:Anthropometry; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D004032:Diet; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D018149:Glucose Intolerance / Q000453:epidemiology / Q000235:genetics; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000235:genetics*; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk
chemical_list: D008055:Lipids