OPRD1 gene polymorphism (rs4654327) as a potential predictor of the effectiveness of long-acting naltrexone in patients with alcohol addiction

Objective. To evaluate the effect of the A>G (rs4654327) polymorphism of the OPRD1 gene on the clinical efficacy of long-acting naltrexone therapy in patients with alcohol addiction. Material and methods. The study included 100 patients with alcohol addiction treated with long-acting naltrexone for 180 days. The duration of remission, the recurrence rate, the completion of the treatment course, the change of pathological alcohol craving (using the Penn Alcohol Craving Scale [PACS]), and the patterns of pathological alcohol craving (PAC) (using the Altshuler scale) were assessed. Genotyping for rs4654327 was performed using real-time polymerase chain reaction. Results. Carriers of the minor G allele (A/G and G/G) exhibited significantly shorter remission (p=0.007), higher recurrence rates (p=0.022), and lower treatment completion rates (p=0.007). The PAC decrease according to PACS was statistically significant after adjustment only in the A/A group (p<0.001). Among G allele carriers, behavioral and affective components were significantly more prevalent in the phenomenological structure of PAC. Conclusion. The rs4654327 polymorphism of the OPRD1 gene may be associated with the variability of the long-acting naltrexone efficacy in patients with alcohol addiction. These preliminary findings suggest that genotyping at this locus could inform personalized anti-recurrence therapy strategies, although validation in larger cohorts is required.