Paper
International Journal of Obesity (2005) 29, 1245–1251. doi:10.1038/sj.ijo.0803024; published online 28 June 2005
Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study
T Salopuro1, L Pulkkinen1, J Lindström2, J G Eriksson2, T T Valle2, H Hämäläinen3, P Ilanne-Parikka4, S Keinänen-Kiukaanniemi5,6, J Tuomilehto2,7, M Laakso8 and M Uusitupa1,9 for the Finnish Diabetes Prevention Study Group
- 1Department of Clinical Nutrition and Food and Health Research Center, University of Kuopio, Kuopio, Finland
- 2Department of Epidemiology and Health Promotion, National Public Health Institute, Diabetes and Genetic Epidemiology Unit, Helsinki, Finland
- 3Research Department, Social Insurance Institution, Turku, Finland
- 4Department of Medicine, Finnish Diabetes Association and Tampere University Hospital, Tampere, Finland
- 5Department of Public Health Science and General Practice, Oulu University Hospital, University of Oulu, Oulu, Finland
- 6Department of Sport Medicine, Oulu Deaconess Institute, Oulu, Finland
- 7Department of Public Health, University of Helsinki, Helsinki, Finland
- 8Department of Medicine, University of Kuopio, Kuopio, Finland
- 9Department of Medicine, Kuopio University Hospital, Kuopio, Finland
Correspondence: T Salopuro, Department of Clinical Nutrition and Food and Health Research Center, University of Kuopio, PO Box 1627, Kuopio FIN-70211, Finland. E-mail: titta.salopuro@uku.fi
Received 7 January 2005; Accepted 28 April 2005; Published online 28 June 2005.
Abstract
OBJECTIVE:
Genetic variation in leptin receptor (LEPR) gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations. We wanted to evaluate the association between LEPR polymorphisms, diabetes risk and body weight in Finnish subjects with impaired glucose tolerance (IGT).
METHODS:
We investigated the associations of the three LEPR polymorphisms (Lys109Arg, Gln223Arg, 3'UTR Del/Ins) with the conversion to type 2 diabetes and the changes in body weight in 507 individuals with IGT participating in the Finnish Diabetes Prevention Study. Participants were randomized to either an intensive diet and exercise intervention group or a control group.
RESULTS:
After 3 years, the odds ratio for the development of type 2 diabetes in individuals in the control group with the Lys109Lys genotype was 2.38-fold higher than in individuals with other genotype combinations (P=0.016). Irrespective of group individuals with the Gln223Gln genotype had higher conversion to type 2 diabetes (OR 2.01 (95% CI 1.03–3.93)) than the Arg223 allele carriers (P=0.042). The risk was more pronounced in the control group than in the intervention group. Individuals having the 3'UTR Del/Del genotype had a slightly higher body weight throughout the study than those with the insertion allele (P=0.020), although no difference in weight change was observed.
CONCLUSION:
Two polymorphisms (Lys109Arg, Gln223Arg) in the extracellular domain of the leptin receptor predicted the conversion to type 2 diabetes in high-risk individuals with IGT. The Del/Ins polymorphism in the 3'UTR of LEPR was associated with body weight.
Keywords:
association, impaired glucose tolerance, intervention, leptin receptor polymorphism, type 2 diabetes
