Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

BMC Medical Genetics

Research Article

Anke Hinney¹  Melanie Wandolski¹  Carla IG Vogel¹  Susann Scherag¹  Jophia Carrie¹  Johannes Hebebrand¹  Günter Brönner²  Timo D Müller³  Winfried Rief⁴  Thomas Illig⁵  Hans-Erich Wichmann⁵  Harald Grallert⁵  André Scherag⁶  Helmut Schäfer⁷  Trang T Nguyen⁷  Brandon H Greene⁷ 

[1] Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany;Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany;Biocenter of the University of Wuerzburg, Wuerzburg, Germany;Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany;Department of Psychiatry, University of Cincinnati, Genome Research Institute, Cincinnati, OH, USA;Department of Clinical Psychology and Psychotherapy, Philipps-University Marburg, Marburg, Germany;Helmholtz Zentrum Muenchen, Deutsches Forschungszentrum fuer Gesundheit und Umwelt, Neuherberg, Germany;Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany;Institute of Medical Biometry and Epidemiology, Philipps-University Marburg, Marburg, Germany;

关键词: Obesity;    Obese Child;    Adult Obesity;    Single Stranded Conformation Polymorphism;    Fatty Acid Amide Hydrolase;   

DOI  :  10.1186/1471-2350-11-2

 received in 2009-04-06, accepted in 2010-01-01,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity.MethodsWe initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity.ResultsThe trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05).ConclusionsAs we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the FAAH variants analyzed here at least do not seem to play a major role in the etiology of obesity within our samples.

【 授权许可】

Unknown   
© Müller et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.