Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism – The Finnish Diabetes Prevention Study

Lappalainen, T.; Kolehmainen, M.; Schwab, U.S.; Tolppanen, A.M.; Stančáková, A.; Lindström, J.; Eriksson, J.G.; Keinänen-Kiukaanniemi, S.; Aunola, S.; Ilanne-Parikka, P.; Herder, C.; Koenig, W.; Gylling, H.; Kolb, H.; Tuomilehto, J.; Kuusisto, J.; Uusitupa, M.; for the Finnish Diabetes Prevention Study Group,

doi:10.1016/j.numecd.2010.01.006

« Previous Next »Nutrition, Metabolism & Cardiovascular Diseases
Volume 21, Issue 9 , Pages 691-698, September 2011

Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism – The Finnish Diabetes Prevention Study

T. Lappalainen
- School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland
- Corresponding author. Tel.: +358 40 355 3607; fax: +358 17 162 792.
M. Kolehmainen
- School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland
U.S. Schwab
- School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland
- Institute of Medicine, Department of Internal Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland
A.M. Tolppanen
- School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland
A. Stančáková
- Institute of Medicine, Department of Internal Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland
J. Lindström
- Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
- Department of Public Health, University of Helsinki, Helsinki, Finland
J.G. Eriksson
- Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
- Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
- Helsinki University Hospital, Unit of General Practice, Helsinki, Finland
- Vasa Central Hospital, Vasa and Folkhälsan Research Unit, Helsinki, Finland
S. Keinänen-Kiukaanniemi
- Oulu University Hospital and Health Centre, Oulu Deaconess Institute and Institute of Health Sciences, University of Oulu, Oulu, Finland
S. Aunola
- National Institute for Health and Welfare, Living Conditions, Health and Wellbeing Unit, Turku, Finland
P. Ilanne-Parikka
- Diabetes Centre of the Finnish Diabetes Association and the Research Unit of Tampere University Hospital, Tampere, Finland
C. Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
W. Koenig
- Department of Internal Medicine II – Cardiology, University of Ulm Medical Centre, Germany
H. Gylling
- School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland
- Institute of Medicine, Department of Internal Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland
H. Kolb
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
J. Tuomilehto
- Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
- Department of Public Health, University of Helsinki, Helsinki, Finland
J. Kuusisto
- Institute of Medicine, Department of Internal Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland
M. Uusitupa
- School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland
for the Finnish Diabetes Prevention Study Group

Received 4 August 2009; received in revised form 18 December 2009; accepted 8 January 2010. published online 20 April 2010.

Abstract

Background and aim

The common single nucleotide polymorphism (SNP) in the FTO (fat mass and obesity associated) gene has been consistently associated with an increased risk of obesity. We investigated whether the SNP rs9939609 (T/A) of the FTO is associated with risk factors of cardiovascular diseases (CVD), including serum levels of C – reactive protein (CRP), the chemokine RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and serum and lipoprotein lipids in the Finnish Diabetes Prevention Study (DPS). Furthermore, we examined whether the rs9939609 increased the CVD risk in the DPS and if these results could be replicated in a larger cross-sectional population-based random sample of Finnish men (the METSIM).

Methods and results

In the DPS, altogether 490 (BMI≥25kg/m²) subjects with impaired glucose tolerance were genotyped for rs9939609. Cardiovascular morbidity and mortality data were collected during the median follow-up of 10.2 years. The replication study was a population-based cross-sectional study of 6214 men.

In the DPS, the AA genotype of rs9939609 was associated, independently of BMI, with increased RANTES (p=0.002) and decreased HDL cholesterol concentrations (p=0.007) in men. During the follow-up, the AA genotype was associated with an adjusted 2.09-fold risk (95% CI 1.17–3.73, p=0.013) of CVD in men. In the METSIM Study, the association with a history of myocardial infarction was replicated in the subgroup of men with type 2 diabetes.