RESUMEN
The brain-derived neurotrophic factor (BDNF) gene may influence eating behavior, body weight and cognitive impairments. We aimed to investigate whether BDNF genetic variability may affect anthropometric and psychological parameters in patients with anorexia or bulimia nervosa (AN, BN) and/or modulate the risk for the disorder. A total of 169 unrelated female patients and 312 healthy controls were genotyped for two common BDNF single-nucleotide polymorphisms (SNPs), Val66Met and C-270T, and several selected tag-SNPs. Associated personality characteristics and psychopathological symptoms were assessed by the EDI-2 and SCL-90R inventories, respectively. No single SNP or haplotype played a relevant role in the risk for AN or BN. The rs16917237 TT genotype was significantly associated with increased weight (74.63 ± 16.58 vs. 57.93 ± 13.02) and body mass index (28.94 ± 6.22 vs. 22.23 ± 4.77) in the BN group after correcting for multiple testing. Haplotype analyses using a sliding window approach with three adjacent SNPs produced four loci of interest. Locus 3 (rs10835210/rs16917237/C-270T) showed a broad impact on the measured psychopathological symptoms. Haplotypes CGC and CGT in this locus correlated with scores in all three scales of the SCL-90R inventory, both in AN and BN patients. In contrast, the results of the EDI-2 inventory were largely unaffected. These preliminary results suggest that variability in the BDNF gene locus may contribute to anthropometric characteristics and also psychopathological symptoms that are common but not exclusive of ED patients.
Asunto(s)
Anorexia Nerviosa/genética , Anorexia Nerviosa/psicología , Factor Neurotrófico Derivado del Encéfalo/genética , Bulimia Nerviosa/genética , Bulimia Nerviosa/psicología , Índice de Masa Corporal , Peso Corporal/genética , Estudios de Casos y Controles , Trastornos del Conocimiento/genética , Conducta Alimentaria/psicología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Polimorfismo de Nucleótido Simple , PsicopatologíaRESUMEN
Dopamine neuronal functions make polymorphisms in dopaminergic pathways good candidates for playing a relevant role in anorexia nervosa (AN) and related psychopathological features. We have analyzed the effect of 8 polymorphisms in genes coding for dopamine receptors (DRD2, DRD3, and DRD4), transporters (DAT1) and metabolizing enzymes (COMT) in 78 women with AN and 186 control subjects. Associated psychopathological characteristics in patients with AN were assessed by the Eating Disorders Inventory Test-2 and SCL-90R self-reported questionnaires. The DRD4 variable number of tandem repeats (VNTR) 7R/7R and DRD4 -616CC genotypes were significantly associated with a greater risk for AN (odds ratio, 3.83; confidence interval, 1.05-13.98; P = 0.04; and odds ratio, 1.74; confidence interval, 1.01-2.97; P = 0.03, respectively). The analysis of physiological parameters in the patients with AN revealed that the short allele of a 120-base pair tandem repeat in the promoter region of the DRD4 gene was associated with higher weight (48.35 ± 6.79 vs 43.95 ± 5.78 kg; Bonferroni, P < 0.05), whereas the DRD4 -521TT genotype was associated with significantly higher body mass index (17.29 ± 2.25 vs 18.13 ± 2.41 kg/m2; Bonferroni, P < 0.05). The DRD4 C-616G and DAT1 VNTR polymorphisms correlated with several psychopathological features in patients with AN. Carriers of the mutant homozygous genotypes scored higher in all but one of the Eating Disorders Inventory Test-2 subscales. After correction for multiple testing, differences in Asceticism scores between DAT1 VNTR genotypes, as well as differences in Drive for Thinness and Body Dissatisfaction between C-616G genotypes remained significant (P < 0.05). The results show that certain genetic alterations in the dopamine pathways are able to modify the risk for AN as well as modulate psychopathological features that are often coupled to this disorder.