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Pediatrics

A gene variant of 11β-hydroxysteroid dehydrogenase type 1 is associated with obesity in children

International Journal of Obesity volume 36, pages 1558–1563 (2012)Cite this article

Subjects

Abstract

Background:

The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme catalyses the regeneration of active cortisol from inert cortisone and plays a critical role in tissue-specific corticosteroid reactions; therefore, 11β-HSD1 is a key molecule associated with the development of obesity. Despite evidence for its role in obesity, no genetic polymorphisms have been significantly associated with the disease per se.

Objective:

The aim of this study was to evaluate whether HSD11B1 gene variants, which have never been studied before, are associated with obesity and its related traits, as well as its relation to biomarkers of inflammation, liver damage and cardiovascular disease in a cohort of Spanish children.

Design:

We performed a prospective case–control study.

Subjects:

A total of 534 children were examined and classified as being obese (n=292) or normal weight (n=242). Anthropometric and biochemical measurements related to obesity, including inflammation, liver damage and cardiovascular disease, were determined. Genomic DNA was extracted and 10 HSD11B1 gene single-nucleotide polymorphisms (SNPs) were genotyped.

Results:

A novel SNP, rs3753519, was strongly associated with obesity and this SNP was the only statistically significant HSD11B1 gene SNP remaining after a Bonferroni correction (odds ratio=1.97 for allelic effect, 95% confidence interval 1.23–3.16; P=0.004 and Bonferroni corrected P=0.046). In addition, this SNP was significantly and positively associated with increased body mass index (BMI), BMI z-score, weight, waist circumference, plasma γ-glutamyl transpeptidase and plasma active plasminogen activator inhibitor 1. The SNP was negatively associated with plasma adiponectin and cortisol after adjusting for sex and age. None of the inflammation biomarkers tested were associated with the risk allele.

Conclusion:

These data, which link an HSD11B1 genotype with both disease prevalence and its related phenotypes, strongly support a role for the rs3753519 polymorphism in the pathogenesis of pediatric-onset obesity.

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Acknowledgements

We thank the children and parents who participated in the study. This work was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I), Instituto de Salud Carlos III-Fondo de Investigación Sanitaria (PI020826, PI051968), the Consejería de Innovación y Ciencia, Junta de Andalucía (P06-CTS 2203) and the Ministerio de Universidades y Tecnología, Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias, Redes temáticas de investigación cooperativa RETIC (Red SAMID RD08/0072/0028).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Centre of Biomedical Research, University of Granada, Granada, Spain

    J Olza, A I Rupérez, A Gil & C M Aguilera

  2. Pediatric Research and Metabolism Unit, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research (IMIBIC), and Unit of Pediatric Endocrinology, Cordoba, Spain

    M Gil-Campos & R Cañete

  3. Pediatric Department, Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Clinic University Hospital of Santiago, University of Santiago de Compostela, Santiago de Compostela, Galicia, Spain

    R Leis & R Tojo

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  1. J Olza
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Correspondence to C M Aguilera.

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Olza, J., Gil-Campos, M., Leis, R. et al. A gene variant of 11β-hydroxysteroid dehydrogenase type 1 is associated with obesity in children. Int J Obes 36, 1558–1563 (2012). https://doi.org/10.1038/ijo.2012.4

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