THE ROLE OF OPRM1 A118G POLYMORPHISMS IN NALTREXONE RESPONSE IN THE TREATMENT OF ALCOHOL USE DISORDER

Abstract Background The prevalence of alcohol use disorder (AUD) has been increased over the past decades in Taiwan. Naltrexone, an opiate antagonist, is currently approved for AUD treatment. However, relapse to heavy or uncontrolled drinking remains common. OPRM1 A118G (Asp40Asn, rs179997), a specific single nucleotide polymorphism (SNP) in the mu opioid receptor gene, moderates naltrexone efficacy. Individuals who carried the A118G G (Asp) allele, approximately 25% in Caucasians and 40-45% in Asians. However, existing evidence largely had focused on Caucasians, leaving the genetic effect unresolved in our Asian people. Aims and Objectives We aimed to assess the clinical variables of patients with AUD, who were treated with naltrexone for 12 weeks, and followed the patients’ drinking outcomes at week 2, 4, 8, 12. In addition, we compared drinking outcomes and psychological assessments between patients with different OPRM1 A118G genotypes. Methods Patients with UAD were provided with naltrexone hydrochloride dosing was titrated from 25 mg per day for the first 3 days to 50 mg per day for the remainder of treatment for 12 weeks. Frequency and quantity of alcohol consumption in the previous 90 days before entering the detoxification treatment was determined using the Time-Line Follow-Back method. We examined average drinks per day, number of drinking days and heavy drinking days per week, and abstinence days during the 12-week study. Alcohol craving was measured by visual analog scale (VAS) and Penn Alcohol Craving Scale (PACS). The individual’ s attitude (self-efficacy or confidence) to abstain from drinking was assessed by Alcohol Abstinence Self-Efficacy scale (AASES). We genotyped OPRM1 A118G genotype (rs179997) for all individuals. Results A total of 94 patients with AUD, who were treated with naltrexone, were recruited into our study. The numbers of patients with OPRM1 A118G AA, AG and GG genotypes are 41, 45, and 8. We combined patients with AG and GG into one group (G-allele carriers) for further analyses. There were no differences in demographic characteristics and drinking history, including mean age, sex distribution, education, age of alcohol tolerance, and duration of drinking history, between G-allele carriers and non- carriers. Regarding drinking outcomes during 12-week naltrexone treatment, we did not find differences in average drinks per day, number of drinking days per week, heavy drinking days per week, and abstinence days between the two groups. Changes of psychological assessments including VAS, PACS, and AASES also did not differ between G-allele carriers and non-carriers. Discussion and Conclusion We did not find any significant genetic effect of OPRM1 A118G on drinking outcomes during 12-week naltrexone treatment.