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


METHODS
We 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 <or= 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values <or2= 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.


RESULTS
The 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).


CONCLUSIONS
As 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.
Müller
Timo D
TD
Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany.
Brönner
Günter
G
Wandolski
Melanie
M
Carrie
Jophia
J
Nguyen
Trang T
TT
Greene
Brandon H
BH
Scherag
André
A
Grallert
Harald
H
Vogel
Carla Ig
CI
Scherag
Susann
S
Rief
Winfried
W
Wichmann
Hans-Erich
HE
Illig
Thomas
T
Schäfer
Helmut
H
Hebebrand
Johannes
J
Hinney
Anke
A
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000581:Amidohydrolases / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D000099252:Fatty Acid Amide Hydrolases