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A gene variant of 11β-hydroxysteroid dehydrogenase type 1 is associated with obesity in children.
- Source :
-
International journal of obesity (2005) [Int J Obes (Lond)] 2012 Dec; Vol. 36 (12), pp. 1558-63. Date of Electronic Publication: 2012 Feb 07. - Publication Year :
- 2012
-
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.<br />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.<br />Design: We performed a prospective case-control study.<br />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.<br />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.<br />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.
- Subjects :
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 metabolism
Adolescent
Age of Onset
Biomarkers blood
Body Composition genetics
Body Mass Index
Cardiovascular Diseases genetics
Cardiovascular Diseases metabolism
Case-Control Studies
Child
Female
Gene Expression Profiling
Genetic Predisposition to Disease
Genotype
Humans
Inflammation blood
Inflammation genetics
Insulin Resistance
Liver metabolism
Male
Obesity epidemiology
Obesity metabolism
Prospective Studies
Spain epidemiology
11-beta-Hydroxysteroid Dehydrogenase Type 1 genetics
Obesity genetics
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5497
- Volume :
- 36
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- International journal of obesity (2005)
- Publication Type :
- Academic Journal
- Accession number :
- 22310475
- Full Text :
- https://doi.org/10.1038/ijo.2012.4