JOURNAL OF MILITARY PHARMACO MEDICINE N05 2022 208 RESEARCH ON THE OPRM1 A118G POLYMORPHISM IN PATIENTS WITH ALCOHOL INDUCED PSYCHOTIC DISORDER Do Xuan Tinh1, Le Dinh Uy1, Dinh Viet Hung1 SUMMARY Obje[.]
JOURNAL OF MILITARY PHARMACO - MEDICINE N05 - 2022 RESEARCH ON THE OPRM1 A118G POLYMORPHISM IN PATIENTS WITH ALCOHOL-INDUCED PSYCHOTIC DISORDER Do Xuan Tinh1, Le Dinh Uy1, Dinh Viet Hung1 SUMMARY Objectives: To characterize the OPRM1 A118G polymorphism in patients with an alcohol-induced psychotic disorder Subjects and methods: A descriptive, cross-sectional study on 31 patients with alcohol-induced psychotic disorder under treatment at the Department of Psychiatry, Military Hospital 103 from April 2021 to March 2022 and 31 control subjects Results: The mean age was 47.45 ± 7.19 The mean daily alcohol intake was 539.68 ± 176.08 mL, and the duration of alcohol use was 16.1 ± 5.94 years The frequency of the G allele was 30.65% The distribution of genotypes of the polymorphisms OPRM1 A118G (AA, AG, GG) was 54.84%, 29.03%, and 16.13%, respectively The difference in allele frequencies and genotype distribution between the alcoholinduced psychotic and the control group was not statistically significant (p > 0.05) The genotype group with the G allele variant (AG+GG) consuming the average amount of alcohol per day was 612.86 ± 218.05 mL, more than the patients with non-G allele (AA) genotype group (p < 0.05) Conclusion: There was no difference in allele frequency and genotype distribution of the OPRM1 A118G polymorphism in alcohol-induced psychotic and the control group However, patients with genotypes containing the G allele variant consumed more alcohol per day than genotypes without this variant *Keywords: Alcohol-induced psychotic disorder; OPRM1 A118G polymorphism INTRODUCTION Alcohol-induced psychotic disorder refers to psychosis that occurs against the background of chronic alcoholism Alcoholism is a complex disease in which both genetic and environmental factors play roles Differences among individuals in the susceptibility Military Hospital 103 Corresponding author: Do Xuan Tinh (doxuantinhbv103@gmail.com) Date received: 02/6/2022 Date accepted: 14/6/2022 208 JOURNAL OF MILITARY PHARMACO - MEDICINE N05 - 2022 to alcohol dependence are almost certainly due to the combined effects of multiple genes, each exerting a small individual effect, with major contributions from gene-gene interactions and geneenvironment interactions The genes in the opioid system are important candidates for the development of alcohol dependence because ethanol activates the brain reward system by increasing the release of an endogenous opioid receptor ligand, β-endorphin The polymorphism A118G within the coding region of OPRM1 is an attractive candidate for study because the change from A to G causes the amino acid change Asn40Asp in the receptor protein, and this change has been reported to increase the binding affinity of the ligand for the receptor [1] Several studies have investigated the association between this polymorphism and the vulnerability to alcohol dependence in various populations, although the results differ among these studies However, there have been no studies on this polymorphism in the Vietnamese population Therefore, we conducted the research: To characterize the OPRM1 A118G polymorphism in patientS with alcohol-induced psychotic disorder to better understand this polymorphism SUBJECTS AND METHODS Subjects The study included 62 subjects, divided into groups: The patient subjects consisted of 31 patients who met DSM-V criteria for alcohol-induced psychotic disorder These patients were under treatment at the Department of Psychiatry, Military Hospital 103, from April 2021 to March 2022 * Exclusion criteria: - The patient had a history of nonalcoholic encephalopathy - The patients had non-alcoholic mental disorders (schizophrenia, mood disorder ) - Patients were addicted to drugs - Patients had endocrine diseases and severe body diseases not caused by alcohol The control subjects consisted of 31 healthy people with low-intake alcohol (The Alcohol Use Disorders Identification Test < 8), similar to the patients in terms of age and gender Methods * Study design: This is a cross-sectional descriptive study For genotyping OPRM1 A118G, using PCR technique with Taq PCR 209 JOURNAL OF MILITARY PHARMACO - MEDICINE N05 - 2022 Master mix sensitive reaction immediately at room conditions combined with 1% agarose electrophoresis to determine the band of the desired size Sanger sequencing identified SNPs on the OPRM1 gene The gene sequencing method was performed at the Department of Anatomy, Military Medical University The data were processed and analyzed on SPSS 22 RESULTS AND DISCUSSION Table 1: Distribution of age Patients Group Control n = 31 Frequency (%) n = 31 Frequency (%) Under 40 years 16.12 12.90 From 40 to 50 years 13 41.94 13 41.94 Over 50 years 13 41.94 14 45.16 Age Average age 47.45 ± 7.19 48.74 ± 8.54 p 0.851 0.522 The results of table showed that psychotic disorder was rare at a young there was no difference in both the age The average age in our study is distribution of numbers, the frequency similar to that of the authors Dang Thi of age groups, and the mean age of the Xuan, Do Ngoc Son (2021) with the two groups with p > 0.05 The mean mean age of patients being 47.6 ± 12.6 age of the study group was 47.45 ± and age group from 40 - 60 accounting 7.19 years, with the majority being for the majority (68.4%) [2], older than over 40 years old (83.8%), indicating the average age of 39.1 ± 6.1 in research that the onset of the alcohol-induced by Narasimha V et al (2019) [3] 210 JOURNAL OF MILITARY PHARMACO - MEDICINE N05 - 2022 Table 2: Distribution of drinking characteristics Group Patients (n = 31) Control (n = 31) 526.77 ± 192.06 Low level of risk AUDIT < 16.1 ± 5.94 Low level of risk AUDIT < Characteristics Amount of alcohol/day (mL) Duration (years) The results of table showed that the average amount of alcohol consumed per day by patients was 526.77 ± 192.06 mL and the duration of alcohol use 16.1 ± 5.94 years, which was much larger than the control group because the control group had a lowrisk of alcohol use (AUDIT < 8) The duration of alcohol use of the patients was similar to that of some authors like Nguyen Van Tuan (2014) with the duration of alcohol use was 14.6 ± 6.5 years [4], which was larger than the author Wilhelm's results with the duration of alcohol use being 12.6 ± 2.9 years [5] Table 3: Allele frequency of the OPRM1 A118G polymorphism Statistical index Group Alcohol induced psychotic The control Allen Amount Frequency (%) A 43 69.35 G 19 30.65 A 37 59.68 G 25 40.32 χ2 = 2.729, p = 0.099 The results in table showed that the frequency of the G variant allele in the alcohol induced psychotic group was 30.65%; in the control group was 40.32%; The difference in allele frequency between the alcohol-induced psychotic group and the control group was not statistically significant with p > 0.05 Our results on the frequency of G allele variation are consistent with the results of some studies such as Deb I et al (2010) with a G variant frequency of 39.6% [1], Kim et al (2004) with a G allele frequency of 211 JOURNAL OF MILITARY PHARMACO - MEDICINE N05 - 2022 39.7% and found no difference in allele frequencies between the control group and the alcoholic group [6], which is higher than the result by Pfeifer P et al (2015) (23%) [7] However, the frequency of this variation varies among different races Our results are also consistent with many publications that the 118G variant is common in Asians, with a frequency ranging from 27% to 48% Table 4: Genotypic distribution of the OPRM1 A118G polymorphism Statistical index Group Genotype n = 31 AA 17 54.84 AG 29.03 GG 16.13 AA 13 41.94 AG 11 35.48 GG 22.58 Alcohol-induced psychotic disorder The control Frequency (%) χ2 = 2.164, p = 0.339 The genotypic distribution of the A118G polymorphism in the study groups followed the Hardy-Weinberg equilibrium with the χ2 test, p > 0.05 (not shown in the table) The above results showed that there were genotypes in both study groups: AA, AG, and GG The distribution of three genotypes AA, AG, GG in the alcohol induced psychotic group was 54.84%, 29.03%, and 16.13%, respectively, and in the control group was 41.94%, 35.48%, 22.58%, respectively There was no difference in genotype distribution of OPRM1 A118G polymorphism between the two study groups with 212 p > 0.05 Our results are not consistent with some publications by author Ishani Deb et al (2010), with genotype distribution AA, AG, and GG in the alcoholism group was 30.18%, 60.37%, 9.43%, respectively, and the distribution was different from the control group with p=0.02 [1], the author Chen D et al (2012) with a meta-analysis and found that the OPRM1 A118G polymorphism could contribute to alcoholism among the Asians [8] However, the difference in sample size, as well as the study subjects of different races, may be the cause of this dissimilarity JOURNAL OF MILITARY PHARMACO - MEDICINE N05 - 2022 Chart 1: The relationship between genotype and alcohol intake The results showed on the graph show that there was a difference in the amount of alcohol consumed between the genotype subgroups (AA and AG+GG) Patients with genotypes containing the G allele variant consumed an average amount of alcohol per day of 612.86 ± 218.05 mL, which is larger than the genotype without the G allele variant with a mean alcohol quantity per day of 432.35 ± 91.75 mL The difference was statistically significant with p < 0.05 (T-test) Our results are similar to those of some authors, such as Gürel Ş.C et al (2016) suggested that carriers of SNP 118G consumed more alcohol and are associated with greater severity of alcoholism [9], author Pfeifer P et al (2015) found that OPRM1 118G allele carriers had a higher tendency of alcohol consumption than those with AA homozygous genotypes [7] and are also consistent with some previous publication that G allele carriers consume higher alcohol consumption than non-carriers of this allele CONCLUSION Research on the OPRM1 A118G polymorphism on patients with alcohol-induced psychotic, we have the following conclusions: - Variants G of the OPRM1 A118G polymorphism appeared with a frequency of 30.65% in the alcohol-induced 213 JOURNAL OF MILITARY PHARMACO - MEDICINE N05 - 2022 psychotic group and 40.32% in the control group The distribution of genotypes AA, AG, and GG in the alcoholic psychotic group was 54.84%, 29.03%, and 16.13%, respectively and in the control group was 41.94%, 35.48%, 22.58%, respectively There was no difference in allele frequency and genotype distribution of the OPRM1 A118G polymorphism in study groups - Patients with genotypes containing the G allele variant consumed a larger average amount of alcohol per day than patients without the G allele variant REFERENCES Deb I., Chakraborty J., Gangopadhyay PK et al (2010) Single-nucleotide polymorphism (A118G) in exon of OPRM1 gene causes alteration in downstream signaling by mu-opioid receptor and may contribute to the genetic risk for addiction J Neurochem; 112(2):486-496 Dang Thi Xuan, Do Ngoc Son (2021) Clinical and laboratory characteristics of severe alcohol withdrawal syndrome treated at the Poison Control Center of Bach Mai Hospital Vietnam Medical Journal Narasimha V.L., Patley R., Shukla L et al (2019) Phenomenology and course of alcoholic hallucinosis J Dual Diagn; 15(3):172-176 214 Nguyen Van Tuan (2014) Clinical study and therapeutic efficacy of cognitive impairment in patients with alcohol induced psychotic Doctoral thesis, Hanoi Medical University, Hanoi Wilhelm J., Frieling H., Hillemacher T et al (2008) Hippocampal volume loss in patients with alcoholism is derived by the consumed type of alcoholic beverage Alcohol Alcohol Oxf Oxfs; 43(3):296-299 Kim S.G., Kim C.M., Kang D.H et al (2004) Association of functional opioid receptor genotypes with alcohol dependence in Koreans Alcohol Clin Exp Res; 28(7):986-990 Pfeifer P., Sariyar M., Eggermann T., et al (2015) Alcohol consumption in healthy oprm1 g allele carriers and its association with impulsive behavior Alcohol Alcohol Oxf Oxfs; 50(4):379-384 Chen D., Liu L., Xiao Y., et al (2012) Ethnic-specific meta-analyses of association between the OPRM1 A118G polymorphism and alcohol dependence among Asians and Caucasians Drug Alcohol Depend; 123(1-3):1-6 Gürel Ş.C., Ayhan Y., Karaaslan ầ et al (2016) à-Opioid Receptor Gene (OPRM1) Polymorphisms A118G and C17T in Alcohol Dependence: A Turkish Sample Turk Psikiyatri Derg Turk J Psychiatry; 27(2):2-4 ... allele CONCLUSION Research on the OPRM1 A118G polymorphism on patients with alcohol- induced psychotic, we have the following conclusions: - Variants G of the OPRM1 A118G polymorphism appeared with. .. studies on this polymorphism in the Vietnamese population Therefore, we conducted the research: To characterize the OPRM1 A118G polymorphism in patientS with alcohol- induced psychotic disorder. .. in table showed that the frequency of the G variant allele in the alcohol induced psychotic group was 30.65%; in the control group was 40.32%; The difference in allele frequency between the alcohol- induced