Original Article
International Journal of Obesity (2008) 32, 1233–1239; doi:10.1038/ijo.2008.68; published online 20 May 2008
Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins
N Y Souren1,2,3, A D Paulussen2,4, A Steyls2,4, R J Loos5,6, A P Stassen4, M Gielen1,2,3, H J Smeets4,7, G Beunen6, R Fagard8, C Derom9, R Vlietinck9, J P Geraedts1,4 and M P Zeegers1,2,3
- 1Department of Complex Genetics, Maastricht University, Maastricht, The Netherlands
- 2Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
- 3Department of Public Health and Epidemiology, Unit of Genetic Epidemiology, University of Birmingham, Birmingham, UK
- 4Division of Clinical Genetics, Academic Hospital Maastricht, Maastricht, The Netherlands
- 5Medical Research Council Epidemiology Unit, Cambridge, UK
- 6Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven, Belgium
- 7Genome Center Maastricht, Maastricht University, Maastricht, The Netherlands
- 8Department of Cardiovascular Diseases, Hypertension and Cardiovascular Rehabilitation Unit, Katholieke Universiteit Leuven, Leuven, Belgium
- 9Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
Correspondence: NYP Souren, Department of Complex Genetics, Maastricht University, Universiteitssingel 50, Maastricht 6200 MD, The Netherlands. E-mail: Nicole.Souren@GEN.unimaas.nl
Received 25 December 2007; Revised 19 March 2008; Accepted 12 April 2008; Published online 20 May 2008.
Abstract
Objective:
Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G>A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins.
Design:
SNPs were genotyped in 396 monozygotic and 232 dizygotic twins (286 men and 342 women, mean age 25 years) recruited from the East Flanders Prospective Twin Survey. Data were analysed using linear mixed models.
Results:
The LEPR K109R SNP was associated with birth weight (KK, KR and RR (95% confidence interval, CI): 2511 (2465–2557), 2575 (2516–2635) and 2726 (2606–2845) gram; Padditive=0.001). Also the LEPR Q223R SNP showed a significant association with weight at birth (QQ, QR and RR (95% CI): 2492 (2431–2554), 2545 (2495–2595) and 2655 (2571–2740) gram; Padditive=0.003). Furthermore, an interaction between the LEPR K109R and the Q223R SNP on birth weight was observed (P=0.014). G allele carriers of the LEP 19G>A SNP had higher high-density lipoprotein (HDL) cholesterol levels compared to 19A homozygotes (GX vs AA (95% CI): 1.62 (1.58–1.66) vs 1.49 (1.40–1.58) mmol l-1; Precessive=0.013).
Conclusions:
This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood. Additionally, these results suggest that the LEP 19G>A SNP affect HDL cholesterol levels.
Keywords:
leptin, leptin receptor, birth weight, type 2 diabetes, single nucleotide polymorphisms
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RESEARCH
International Journal of Obesity Original Article
