Influence of dopamine polymorphisms on the risk for anorexia nervosa and associated psychopathological features.

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.