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Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study

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.

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Acknowledgements

This work has been financially supported by grants from the Academy of Finland (no. 40758 to MU; 38387 and 46558 to JT; 73566 to SK-K), the EVO-fund of the Kuopio University Hospital (no. 5106 to MU; 5194 to ML), the Ministry of Education of Finland and the Finnish Diabetes Research Foundation, Yrjö Jahnsson Foundation and Juho Vainio Foundation.

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Salopuro, T., Pulkkinen, L., Lindström, J. et al. Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study. Int J Obes 29, 1245–1251 (2005). https://doi.org/10.1038/sj.ijo.0803024

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