Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes
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Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes. / Oskari Kilpeläinen, Tuomas; Lakka, T A; Laaksonen, D E; Laukkanen, O; Lindström, J; Eriksson, J G; Valle, T T; Hämäläinen, H; Aunola, S; Ilanne-Parikka, P; Keinänen-Kiukaanniemi, S; Tuomilehto, J; Uusitupa, M; Laakso, M; Finnish Diabetes Prevention Study Group.
In: Physiological Genomics, Vol. 31, No. 2, 22.10.2007, p. 264-72.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes
AU - Oskari Kilpeläinen, Tuomas
AU - Lakka, T A
AU - Laaksonen, D E
AU - Laukkanen, O
AU - Lindström, J
AU - Eriksson, J G
AU - Valle, T T
AU - Hämäläinen, H
AU - Aunola, S
AU - Ilanne-Parikka, P
AU - Keinänen-Kiukaanniemi, S
AU - Tuomilehto, J
AU - Uusitupa, M
AU - Laakso, M
AU - Finnish Diabetes Prevention Study Group
PY - 2007/10/22
Y1 - 2007/10/22
N2 - Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N = 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6- to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P = 0.022-0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT.
AB - Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N = 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6- to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P = 0.022-0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT.
KW - ATP-Binding Cassette Transporters
KW - Combined Modality Therapy
KW - Diabetes Mellitus, Type 2
KW - Disease Progression
KW - Exercise Therapy
KW - Exons
KW - Female
KW - Finland
KW - Genetic Predisposition to Disease
KW - Glucose Intolerance
KW - Glucose Transporter Type 2
KW - Health Promotion
KW - Humans
KW - Insulin
KW - Intervention Studies
KW - Male
KW - Middle Aged
KW - Overweight
KW - Polymorphism, Single Nucleotide
KW - Potassium Channels
KW - Potassium Channels, Inwardly Rectifying
KW - Promoter Regions, Genetic
KW - Receptors, Drug
KW - Risk
KW - Weight Loss
U2 - 10.1152/physiolgenomics.00036.2007
DO - 10.1152/physiolgenomics.00036.2007
M3 - Journal article
C2 - 17636114
VL - 31
SP - 264
EP - 272
JO - Physiological Genomics
JF - Physiological Genomics
SN - 1094-8341
IS - 2
ER -
ID: 46280934