Abstract
Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are the three most common eating disorders (EDs). Their etiopathogenesis is multifactorial where both the environmental and genetic factors contribute to the disease outcome and severity. Several polymorphisms in genes involved in the dopaminergic pathways seem to be relevant in the susceptibility to EDs, but their role has not been fully elucidated yet. In this study, we have analyzed the association between selected common polymorphisms in the DRD2 and DRD4 genes in a large cohort of Italian patients affected by AN (n = 332), BN (n = 122), and BED (n = 132) compared to healthy controls (CTRs) (n = 172). Allelic and genotypic frequencies have been also correlated with the main psychopathological and clinical comorbidities often observed in patients. Our results showed significant associations of the DRD2-rs6277 single nucleotide polymorphism (SNP) with AN and BN, of the DRD4-rs936461 SNP with BN and BED and of DRD4 120-bp tandem repeat (TR) polymorphism (SS plus LS genotypes) with BED susceptibility. Moreover, genotyping of DRD4 48-bp variable number TR (VNTR) identified the presence of ≥7R alleles as risk factors to develop each type of EDs. The study also showed that ED subjects with a history of drugs abuse were characterized by a significantly higher frequency of the DRD4 rs1800955 TT genotype and DRD4 120-bp TR short-allele. Our findings suggest that specific combinations of variants in the DRD2 and DRD4 genes are predisposing factors not only for EDs but also for some psychopathological features often coupled specifically to AN, BN, and BED. Further functional research studies are needed to better clarify the complex role of these proteins and to develop novel therapeutic compounds based on dopamine modulation.
Highlights
Eating disorders (EDs), divided into eight categories according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) [1], are serious psychiatric illnesses and they have been increased over the past 50 years [2]
Genes coding for enzymes, receptors, and transporters involved in DA pathways have been considered crucial candidates for genetic association studies in patients affected by EDs, including Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED)
Several studies have demonstrated a correlation between EDs and an single nucleotide polymorphism (SNP) located in the promoter region of DRD4 (C521T, rs1800955); notably, the C allele was associated with personality traits related to AN, and in particular, is correlated with perfectionism [42, 43]
Summary
Eating disorders (EDs), divided into eight categories according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) [1], are serious psychiatric illnesses and they have been increased over the past 50 years [2]. DA release is associated with the duration of meal consumption and dysfunction of DA receptors has been suggested to predispose to EDs by altering the feeding behavior [26], by disturbing reward associated with food intake [27], and by distorting of body shape and image [28] Based on these evidences, genes coding for enzymes, receptors, and transporters involved in DA pathways have been considered crucial candidates for genetic association studies in patients affected by EDs, including AN, BN, and BED. The most interesting allele is 7R that has been shown to reduce the expression of the receptor [46] and its affinity for DA [47] This repeated polymorphism has been strongly associated with overeating, obesity [48–51], drug abuse, and related comorbidities [19]. Different SNPs in the DRD4 gene may predispose to BN, aggravate its clinical course, or reflect other comorbidities in these patients [49]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
