Impact of Variability in the Delta Opioid Receptor (OPRD1) Gene on Body Mass Index and Psychometric Characteristics of Eating Disorders Patients

Objectives: This study aimed to investigate whether genetic variations in the OPRD1 gene affect psychopathological symptoms and personality dimensions in eating disorders (ED) patients and/or contribute to ED risk. Methods: The study involved 221 female patients with anorexia nervosa (AN), 88 with bulimia nervosa (BN) and 396 controls. Sixteen tag-SNPs in OPRD1 were identified. Psychometric evalu-ations were conducted using the Symptom Checklist 90 Revised (SCL-90R) and the Eating Dis-orders Inventory Test-2 (EDI-2). P-values obtained by regression models were corrected for mul-tiple testing by the FDR method. Results: In AN patients, genotypes rs204077TT and rs169450TT were linked to lower BMI values (FDR-q=0.035 and 0.017, respectively), as was rs2234918 in a log-additive model (BMI: 18.0±0.28, 17.22±0.18 and 16.59±0.39 for TT, TC and CC carriers, FDR-q=0.012). Additionally, AN patients carrying the rs72665504AA genotype had higher scores in Interpersonal distrust (FDR-q=0.030), whilst BN carriers of rs513269TT and rs2873795TT showed lower scores in Ineffectiveness (FDR-q=0.041 and FDR-q=0.021). In the AN group, BMI correlated with variability in a distal haplotype (rs508448/rs204077/rs223491, FDR-q=0.028), which was also associated with the global PST index of SCL-90R (FDR-q=0.048). Associations were more noticeable in BN patients; again, the distal region of the gene was linked to EDI-2 total scores (FDR-q=0.004-0.048 for the four last haplotypes) and two global SCL-90R indices (GSI: FDR-q=0.011 and PSDI: FDR-q=0.003 for the last s204077/rs2234918/rs169450 combination). No associations with ED risk were observed. Conclusions: Genetic variation in the OPRD1 gene, particularly in its distal region, is associated with BMI and psychopathological comorbidities in ED patients.