Association Between DRD2 and DRD4 Polymorphisms and Eating Disorders in an Italian Population

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.

Analysis of Factors Associated with Outcomes of Bariatric Surgery: rs1800497 ANKK1, rs1799732 DRD2 Genetic Polymorphisms, Eating Behavior, Hedonic Hunger, and Depressive Symptoms

“…Allele Taq1A is associated with obesity (17,49), hedonic hunger (17), and binge eating disorder (28) and was also associated with a higher risk of abnormal glucose, triglycerides and VLDL levels in Mexican subjects (26). Patients with BED homozygous for the A1 allele of ANKK1-rs1800497 exhibited a signi cant association with binge eating episodes (OR = 7.69; 95% CI 2.08-29.4; p = 0.001) (50). In our group, the carriers of the A1/A1 genotype showed higher glucose levels and TFEQ-R18 scores, which has been demonstrated to be a valid instrument to measure eating behavior, including dietary control, in individuals with normal weight, as in individuals with obesity (32) (33).…”

SLC6A4 DNA Methylation Levels and Serum Kynurenine/Tryptophan Ratio in Eating Disorders: A Possible Link with Psychopathological Traits?

“…Exclusion criteria for the admission, determined before psychological test [ 41 ], included mental retardation, dementia, schizophrenia, Turner’s syndrome, other neurological disorders, and underlying endocrine pathologies. CTRs inclusion criteria include never having been diagnosed with any previous EDs and/or familiarity with EDs, any psychiatric disorders and/or familiarity, and having normal BMI for their whole life (range 18.5–24.9 kg/m 2 ).…”

Food Reward Alterations during Obesity Are Associated with Inflammation in the Striatum in Mice: Beneficial Effects of Akkermansia muciniphila

“…This hypofunctioning of the dopamine pathway leads to altered hedonic and motivational behavior feeding inducing unbiased responses to hedonic food [ 9 , 16 , 17 ]. Importantly, some human Drd2 and Drd4 genes’ polymorphisms are associated with eating disorders [ 18 , 19 , 20 ]. The TaqIA1 allele polymorphism is associated with a decrease in striatal Drd2 abundance up to 40% [ 14 ].…”