Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes

Tuomas Oskari Kilpeläinen; T A Lakka; D E Laaksonen; O Laukkanen; J Lindström; J G Eriksson; T T Valle; H Hämäläinen; S Aunola; P Ilanne-Parikka; S Keinänen-Kiukaanniemi; J Tuomilehto; M Uusitupa; M Laakso; Finnish Diabetes Prevention Study Group

doi:10.1152/physiolgenomics.00036.2007

Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes

Tuomas Oskari Kilpeläinen, T A Lakka, D E Laaksonen, O Laukkanen, J Lindström, J G Eriksson, T T Valle, H Hämäläinen, S Aunola, P Ilanne-Parikka, S Keinänen-Kiukaanniemi, J Tuomilehto, M Uusitupa, M Laakso, Finnish Diabetes Prevention Study Group

33 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Physiological Genomics
Vol/bind	31
Udgave nummer	2
Sider (fra-til)	264-72
Antal sider	9
ISSN	1094-8341
DOI	https://doi.org/10.1152/physiolgenomics.00036.2007
Status	Udgivet - 22 okt. 2007

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10.1152/physiolgenomics.00036.2007

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Oskari Kilpeläinen, T., 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 (2007). Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes. Physiological Genomics, 31(2), 264-72. https://doi.org/10.1152/physiolgenomics.00036.2007

Oskari Kilpeläinen, T, Lakka, TA, Laaksonen, DE, Laukkanen, O, Lindström, J, Eriksson, JG, Valle, TT, Hämäläinen, H, Aunola, S, Ilanne-Parikka, P, Keinänen-Kiukaanniemi, S, Tuomilehto, J, Uusitupa, M, Laakso, M & Finnish Diabetes Prevention Study Group 2007, 'Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes', Physiological Genomics, bind 31, nr. 2, s. 264-72. https://doi.org/10.1152/physiolgenomics.00036.2007

@article{8d0fb153515f4cfea51e6dc689b20c3c,

title = "Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes",

abstract = "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.",

keywords = "ATP-Binding Cassette Transporters, Combined Modality Therapy, Diabetes Mellitus, Type 2, Disease Progression, Exercise Therapy, Exons, Female, Finland, Genetic Predisposition to Disease, Glucose Intolerance, Glucose Transporter Type 2, Health Promotion, Humans, Insulin, Intervention Studies, Male, Middle Aged, Overweight, Polymorphism, Single Nucleotide, Potassium Channels, Potassium Channels, Inwardly Rectifying, Promoter Regions, Genetic, Receptors, Drug, Risk, Weight Loss",

author = "{Oskari Kilpel{\"a}inen}, Tuomas and Lakka, {T A} and Laaksonen, {D E} and O Laukkanen and J Lindstr{\"o}m and Eriksson, {J G} and Valle, {T T} and H H{\"a}m{\"a}l{\"a}inen and S Aunola and P Ilanne-Parikka and S Kein{\"a}nen-Kiukaanniemi and J Tuomilehto and M Uusitupa and M Laakso and {Finnish Diabetes Prevention Study Group}",

year = "2007",

month = oct,

day = "22",

doi = "10.1152/physiolgenomics.00036.2007",

language = "English",

volume = "31",

pages = "264--72",

journal = "Physiological Genomics",

issn = "1094-8341",

publisher = "American Physiological Society",

number = "2",

}

TY - JOUR

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

SN - 1094-8341

VL - 31

SP - 264

EP - 272

JO - Physiological Genomics

JF - Physiological Genomics

IS - 2

ER -

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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