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

Tuomas Oskari Kilpeläinen; Timo A Lakka; David E Laaksonen; Ursula Mager; Titta Salopuro; Agata Kubaszek; Boryana Todorova; Olli Laukkanen; Jaana Lindström; Johan G Eriksson; Helena Hämäläinen; Sirkka Aunola; Pirjo Ilanne-Parikka; Sirkka Keinänen-Kiukaanniemi; Jaako Tuomilehto; Markku Laakso; Matti Uusitupa; Finnish Diabetes Prevention Study Group

doi:10.1016/j.metabol.2007.10.022

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

Tuomas Oskari Kilpeläinen, Timo A Lakka, David E Laaksonen, Ursula Mager, Titta Salopuro, Agata Kubaszek, Boryana Todorova, Olli Laukkanen, Jaana Lindström, Johan G Eriksson, Helena Hämäläinen, Sirkka Aunola, Pirjo Ilanne-Parikka, Sirkka Keinänen-Kiukaanniemi, Jaako Tuomilehto, Markku Laakso, Matti Uusitupa, Finnish Diabetes Prevention Study Group

34 Citations (Scopus)

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.

Original language	English
Journal	Metabolism
Volume	57
Issue number	3
Pages (from-to)	428-36
Number of pages	9
ISSN	0026-0495
DOIs	https://doi.org/10.1016/j.metabol.2007.10.022
Publication status	Published - Mar 2008

Keywords

Anthropometry
Blood Pressure
Body Weight
Diabetes Mellitus, Type 2
Diet
Female
Finland
Gene Frequency
Genotype
Glucose Intolerance
Homeostasis
Humans
Lipids
Male
Metabolic Syndrome X
Middle Aged
Motor Activity
Polymorphism, Single Nucleotide
Risk

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Oskari Kilpeläinen, T., Lakka, T. A., Laaksonen, D. E., Mager, U., Salopuro, T., Kubaszek, A., Todorova, B., Laukkanen, O., Lindström, J., Eriksson, J. G., Hämäläinen, H., Aunola, S., Ilanne-Parikka, P., Keinänen-Kiukaanniemi, S., Tuomilehto, J., Laakso, M., Uusitupa, M., & Finnish Diabetes Prevention Study Group (2008). 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. Metabolism, 57(3), 428-36. https://doi.org/10.1016/j.metabol.2007.10.022

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. / Oskari Kilpeläinen, Tuomas; Lakka, Timo A; Laaksonen, David E et al.
In: Metabolism, Vol. 57, No. 3, 03.2008, p. 428-36.

Research output: Contribution to journal › Journal article › Research › peer-review

Oskari Kilpeläinen, T, Lakka, TA, Laaksonen, DE, Mager, U, Salopuro, T, Kubaszek, A, Todorova, B, Laukkanen, O, Lindström, J, Eriksson, JG, Hämäläinen, H, Aunola, S, Ilanne-Parikka, P, Keinänen-Kiukaanniemi, S, Tuomilehto, J, Laakso, M, Uusitupa, M & Finnish Diabetes Prevention Study Group 2008, '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', Metabolism, vol. 57, no. 3, pp. 428-36. https://doi.org/10.1016/j.metabol.2007.10.022

Oskari Kilpeläinen T, Lakka TA, Laaksonen DE, Mager U, Salopuro T, Kubaszek A et al. 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. Metabolism. 2008 Mar;57(3):428-36. doi: 10.1016/j.metabol.2007.10.022

Oskari Kilpeläinen, Tuomas ; Lakka, Timo A ; Laaksonen, David E et al. / 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. In: Metabolism. 2008 ; Vol. 57, No. 3. pp. 428-36.

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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.",

keywords = "Anthropometry, Blood Pressure, Body Weight, Diabetes Mellitus, Type 2, Diet, Female, Finland, Gene Frequency, Genotype, Glucose Intolerance, Homeostasis, Humans, Lipids, Male, Metabolic Syndrome X, Middle Aged, Motor Activity, Polymorphism, Single Nucleotide, Risk",

author = "{Oskari Kilpel{\"a}inen}, Tuomas and Lakka, {Timo A} and Laaksonen, {David E} and Ursula Mager and Titta Salopuro and Agata Kubaszek and Boryana Todorova and Olli Laukkanen and Jaana Lindstr{\"o}m and Eriksson, {Johan G} and Helena H{\"a}m{\"a}l{\"a}inen and Sirkka Aunola and Pirjo Ilanne-Parikka and Sirkka Kein{\"a}nen-Kiukaanniemi and Jaako Tuomilehto and Markku Laakso and Matti Uusitupa and {Finnish Diabetes Prevention Study Group}",

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doi = "10.1016/j.metabol.2007.10.022",

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journal = "Metabolism",

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TY - JOUR

T1 - 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

T2 - The Finnish Diabetes Prevention Study

AU - Oskari Kilpeläinen, Tuomas

AU - Lakka, Timo A

AU - Laaksonen, David E

AU - Mager, Ursula

AU - Salopuro, Titta

AU - Kubaszek, Agata

AU - Todorova, Boryana

AU - Laukkanen, Olli

AU - Lindström, Jaana

AU - Eriksson, Johan G

AU - Hämäläinen, Helena

AU - Aunola, Sirkka

AU - Ilanne-Parikka, Pirjo

AU - Keinänen-Kiukaanniemi, Sirkka

AU - Tuomilehto, Jaako

AU - Laakso, Markku

AU - Uusitupa, Matti

AU - Finnish Diabetes Prevention Study Group

PY - 2008/3

Y1 - 2008/3

N2 - 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.

AB - 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.

KW - Anthropometry

KW - Blood Pressure

KW - Body Weight

KW - Diabetes Mellitus, Type 2

KW - Diet

KW - Female

KW - Finland

KW - Gene Frequency

KW - Genotype

KW - Glucose Intolerance

KW - Homeostasis

KW - Humans

KW - Lipids

KW - Male

KW - Metabolic Syndrome X

KW - Middle Aged

KW - Motor Activity

KW - Polymorphism, Single Nucleotide

KW - Risk

U2 - 10.1016/j.metabol.2007.10.022

DO - 10.1016/j.metabol.2007.10.022

M3 - Journal article

C2 - 18249219

SN - 0026-0495

VL - 57

SP - 428

EP - 436

JO - Metabolism

JF - Metabolism

IS - 3

ER -