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Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

An Erratum to this article was published on 11 August 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.

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Acknowledgements

This work was financially supported by the Dutch Diabetes Research Foundation (DFN 2002.00.15), the Netherlands Organization for Scientific Research (NWO; 2006/04581/IB), Stichting Simonsfonds and the National Fund for Scientific Research Belgium (G.3.0269.97; G.0383.03). The EFPTS has been partly supported by grants from Funds of Scientific Research Flanders and by the Association for Scientific Research in Multiple Births (VZW Twins). We are grateful to all twins participating in this study. We thank Ingeborg Berckmoes, Annie Roossens, Lut De Zeure, Margaret Van Heuverswyn and An Voets for fieldwork and technical assistance.

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Correspondence to N Y Souren.

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Supplementary Information accompanies the paper on International Journal of Obesity website (http://www.nature.com/ijo)

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Souren, N., Paulussen, A., Steyls, A. et al. Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins. Int J Obes 32, 1233–1239 (2008). https://doi.org/10.1038/ijo.2008.68

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