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  • Population Study Article
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Association of DLK1 SNPs with body mass index and plasma lipid levels in children

Pediatric Research volume 98, pages 1731–1736 (2025)Cite this article

Abstract

Background

The DLK1 human gene encodes for the transmembrane EGF-like repeat-containing protein DLK1, which acts as a modulator of adipogenesis. A role for DLK1 in energy metabolism and lipid homeostasis has been suggested and DLK1 gene variants have been related to pubertal development.

Objective

The aim of this study was to uncover DLK1 SNPs in a cohort of children and analyze their relationship with anthropometric and biochemical variables.

Methods

Our population-based sample comprises 1237 healthy 6-to-8-year-old Caucasian children. The presence of five DLK1 SNPs (rs1802710, rs876374, rs7155375, rs57098752, and rs7149242) was analyzed by Real-Time PCR, using predesigned TaqMan™ Genotyping Assays.

Results

We observed that the SNPs rs1802710 and rs876374 were associated with BMI, and the prevalence of these two SNPs was different in normal-weight children compared to children with obesity. Related to biochemical variables, we found a significant association of the SNPs rs1802710, rs876374, and rs57098752 and their combination with Apo-B plasma concentrations after adjusting by BMI and sex. The SNPs rs1802710 and rs57098752 were also significantly associated with plasma levels of LDL-C and HDL-C, respectively.

Conclusion

Our study reveals that DLK1 gene variants may influence both body weight and lipid homeostasis, affecting particularly to the Apo-B biology, in children.

Impact

  • DLK1 polymorphisms are associated with BMI and with lipid levels, independently of BMI, early in life.

  • Our data add to the existing literature the evidence that DLK1 gene variants impact on lipid metabolism.

  • The confirmation at the population level that DLK1 genetic variants are associated with anthropometric and lipid variables sustains the role of DLK1 in obesity and related disorders and should lead to further studies aimed at clarifying this effect.

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Fig. 1: Prevalence of DLK1 SNPs rs1802710 and rs876374 genotypes in children with normal weight (NW), overweight (OW), and obesity (OB).
Fig. 2: Plasma lipid levels according to genotype for each DLK1 polymorphism (rs1802710, rs57098752, and rs876374) adjusted for sex and BMI.

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Data availability

The datasets analysed during the current study are available from the corresponding author on reasonable request and with permission of the Jiménez Díaz Foundation Clinical Research Ethics Committee.

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Acknowledgements

This article is dedicated to the late Prof. Manuel de Oya as the warmest homage to his memory. Prof. de Oya designed the Four Province Study. This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project FIS-PI22/00498 and co-funded by the European Union. Olga Pomares is recipient of a research contract from Carlos III Institute of Health (pFIS).

Author information

Authors and Affiliations

  1. Lipid Research Laboratory, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain

    Olga Pomares, Claudia Vales-Villamarín, Iris Pérez-Nadador & Carmen Garcés

  2. Department of Inorganic and Organic Chemistry and Biochemistry, Pharmacy School, University of Castilla-La Mancha, Albacete, Spain

    Jorge Laborda

  3. Department of Pediatrics, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain

    Francisco. J. Mejorado-Molano, Alejandro Parra-Rodríguez & Leandro Soriano-Guillén

  4. Epidemiological Research Unit, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain

    Ignacio Mahillo-Fernández

Authors
  1. Olga Pomares
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  2. Jorge Laborda
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  8. Leandro Soriano-Guillén
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Contributions

Conception and design: C.G.; Acquisition of data: O.P., C.V-V., I.P.-N., F.J.M.-M., A.P.-R., and I.M.F.; Analysis and interpretation of data: O.P., J.L., and C.G.; Original draft preparation: C.G.; Critical revision: O.P., J.L., C.V-V., I.P.-N., F.J.M-M., A.P.-R., I.M.-F. and L.S.-G. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Carmen Garcés.

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The authors declare no competing interests.

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Written informed consent to participate in this study was provided by the participant’s legal guardian/next of kin.

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Pomares, O., Laborda, J., Vales-Villamarín, C. et al. Association of DLK1 SNPs with body mass index and plasma lipid levels in children. Pediatr Res 98, 1731–1736 (2025). https://doi.org/10.1038/s41390-025-04005-0

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