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GENETIC ADDICTION RISK SCORE (GARS) ANALYSIS: EXPLORATORY DEVELOPMENT OF POLYMORPHIC RISK ALLELES IN POLY-DRUG ADDICTED MALES

Keywords: Genetic Addiction Risk Score (GARS) , polymorphic genes , Neurotransmitters , Dopamine , Reward Deficiency Syndrome (RDS)

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Abstract:

There is a need to classify patients at genetic risk for drug seeking behavior prior to or upon entry to residential and or non-residential chemical dependency programs. We have determined based on a literature review, that there are seven risk alleles associated with six candidate genes that were studied in this patient population of recovering poly-drug abusers. To determine risk severity of these 26 patients we calculated the percentage of prevalence of the risk alleles and provided a severity score based on percentage of these alleles. Subjects carry the following risk alleles: DRD2=A1; SLC6A3 (DAT) =10R; DRD4=3R or 7R; 5HTTlRP = L or LA; MAO= 3R; and COMT=G. As depicted in table 2 low severity (LS) = 1-36%; Moderate Severity =37-50%, and High severity = 51-100%. We studied two distinct ethnic populations group 1 consisted of 16 male Caucasian psycho stimulant addicts and group 2 consisted of 10 Chinese heroin addicted males. Based on this model the 16 subjects tested have at least one risk allele or 100%. Out of the 16 subjects we found 50% (8) HS; 31% (5) MS; and 19% LS (3 subjects). These scores are then converted to a fraction and then represented as a Genetic Addiction Risk Score (GARS) whereby we found the average GARS to be: 0.28 low severity, 0.44 moderate severity and 0.58 high severity respectively. Therefore, using this GARS we found that 81% of the patients were at moderate to high risk for addictive behavior. Of particular interest we found that 56% of the subjects carried the DRD2 A1 allele (9/16). Out of the 9 Chinese heroin addicts [one patient not genotyped] (group 2) we found 11% (1) HS; 56% (5) MS; and 33% LS (3 subjects). These scores are then converted to a fraction and then represented as GARS whereby we found the average GARS to be: 0.28 Low Severity; 0.43 moderate severity and 0.54 high severity respectively. Therefore, using GARS we found that 67% of the patients were at moderate to high risk for addictive behavior. Of particular interest we found that 56% of the subjects carried the DRD2 A1 allele (5/9) similar to group 1. Statistical analysis revealed that the groups did not differ in terms of overall severity (67 vs. 81%) in these two distinct populations. Combining these two independent study populations reveal that subjects entering a residential treatment facility for poly-drug abuse carry at least one risk allele (100%). We found 74% of the combined 25 subjects (Caucasian and Chinese) had a moderate to high GARS. Confirmation of these exploratory results and development of mathematical predictive values of these risk

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