Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: evidence for synergistic effects.
Endocannabinoids modulate eating behavior; hence, endocannabinoid genes may contribute to the biological vulnerability to eating disorders. The rs1049353 (1359 G/A) single nucleotide polymorphism (SNP) of the gene coding the endocannabinoid CB1 receptor (CNR1) and the rs324420 (cDNA 385C to A) SNP of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, have been suggested to have functional effects on mature proteins. Therefore, we explored the possibility that those SNPs were associated to anorexia nervosa and/or bulimia nervosa. The distributions of the CNR1 1359 G/A SNP and of the FAAH cDNA 385C to A SNP were investigated in 134 patients with anorexia nervosa, 180 patients with bulimia nervosa and 148 normal weight healthy controls. Additive effects of the two SNPs in the genetic susceptibility to anorexia nervosa and bulimia nervosa were also tested. As compared to healthy controls, anorexic and bulimic patients showed significantly higher frequencies of the AG genotype and the A allele of the CNR1 1359 G/A SNP. Similarly, the AC genotype and the A allele of the FAAH cDNA 385C to A SNP were significantly more frequent in anorexic and bulimic individuals. A synergistic effect of the two SNPs was evident in anorexia nervosa but not in bulimia nervosa. Present findings show for the first time that the CNR1 1359 G/A SNP and the FAAH cDNA 385C to A SNP are significantly associated to anorexia nervosa and bulimia nervosa, and demonstrate a synergistic effect of the two SNPs in anorexia nervosa.
Monteleone
P
P
Department of Psychiatry, University of Naples SUN, Largo Madonna delle Grazie, 80138 Naples, Italy. monteri@tin.it
Bifulco
M
M
Di Filippo
C
C
Gazzerro
P
P
Canestrelli
B
B
Monteleone
F
F
Proto
M C
MC
Di Genio
M
M
Grimaldi
C
C
Maj
M
M
D000328:Adult; D000581:Amidohydrolases / Q000235:genetics*; D000856:Anorexia Nervosa / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D052018:Bulimia Nervosa / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D004252:DNA Mutational Analysis; D063388:Endocannabinoids; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005819:Genetic Markers; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases