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Genetics of Addiction

BY: Chandra Kala | Category: Genetics | Submitted: 2012-11-16 06:28:13
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Article Summary: "Addiction is a brain disorder that is common and economically costly habit to the individual. Drug addiction is now linked to many genetic markers and is important in success of treatment for drug addiction. Not only the mental strength of the individual is sufficient to recover from addiction, there is also blueprint in the g.."


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Addiction is a brain disorder that is common and economically costly habit to the individual. Addictions are disorders that are often relapsing and chronic. Contributions of Genetics in the area of addictions is significant and with Genome-Wide Association Studies (GWAS) applications, several chromosomal loci and genes are now found associated with addiction of many addicting substances such as alcohol, tobacco, and opioid drugs etc. Many single nucleotide polymorphisms (SNPs) are found associated with addictions and few SNPs of genes are found associated with many addictions phenomenon.

OPRM1 (mu opioid receptor) gene product is the receptor for opioids (heroin and morphine) and is critical for opioid addictions. Genetic variations in the OPRM1 gene have been attributed to the observed individual differences in response to opiate drugs. OPRM1 polymorphism Asn40Asp (A118G, rs1799971) has been extensively studied for its role with opioid dependence (OD). OPRM1 rs1799971 SNP was also associated with morphine response variability in pharmacogenetics as well with chronic pain which required analgesic in higher doses. PORK1 gene with G36T (rs1051660) SNP was associated with opiate addiction and cocaine dependence. PDYN gene with three SNPs (rs910080, rs910079, and rs2235749) was found associated with cocaine dependence and alcohol dependence. MC2R, another G protein coupled receptor with SNPs rs2186944, rs28926182, and rs4797824 were associated with protective effect against development of heroin addiction. A substitution Val158Met SNP of COMT gene involved in the metabolism of neurotransmitters like dopamine, has been found associated with cocaine dependence, further it was found that 158met allele is sex specific and males with this allele were associated with obsessive compulsive disorder. It was also found the COMT G472A SNP was associated with opiate addiction. Typtophan hydroxylase (TPH) isoforms TPH1 and TPH2 are associated with addictions. TPH1 gene rs1799913 and rs1800532 SNPs were found associated with several addictions including alcohol dependence. TPH2 rs4290270 and rs7963720 SNPs were associated with heroin addiction. HTR1B gene rs6296 (G861C) was also associated with alcoholics.

Methadone is the synthetic compound which is used in treatment for drug addictions. The success of treatments depends on the individual dose requirement. Several cytochrome P450 enzymes such as CYP3A4, CYP2B6, and CYP2D6 are involved in the methadone absorption and metabolism. Based on the metabolism of the medicine by individuals they are classified as ultrarapid metabolizers, moderate metabolizers, and poor metabolizers, etc. Ultrarapid metabolizers are associated with unsuccessful in treatment with methadone treatment as the medicine is metabolized rapidly in the individuals there by eliminating the effects of medicine. ABCB1 gene codes for the P-gp protein which influences methadone distribution in tissues. Variations in ABCB1 genes such as rs1045642 (C3435T), rs1128503, and rs2032582 were found associated with lower doses of methadone in methadone maintenance treatment.

Drug addiction is now linked to many genetic markers genes; among which genes such as OPRM1, PDYN, PORK1, COMT, and TPH are important and similarly cytochrome P450 3A4, 2B6, 2D6, and ABCB1 genes are important in success of treatment for drug addiction. Not only the mental strength of the individual is sufficient to recover from addiction, there is also blueprint in the genome which decides the success of the treatment. We can now clearly say genetic markers have major role in the success for the treatment for individuals of drug addicts.

Many recent researches have pointed with SNPs to Drug addictions, but further research is required to validate in different populations. Several SNPs found associated with drug addictions are ethnicity specific and hence studies involving larger population with mixed ethnicity and gender are required to establish common gene variants. Further it is also recommended to study the combined effect of different polymorphisms within single gene and also across different genes. GWAS and Meta-analysis studies are critical to evaluate the role of individual SNPs with drug addiction and treatment. The genetic variants / markers now available by comparing the sequence of individuals/ study groups with the reference genome sequence obtained from the human genome project will go a long way in developing personalized medicine, which aims at curing diseases, treatment for drug addictions, etc., with optimum usage of right medicine. The studies on the variations of genes will help to select correct medicines and doses of it, which help in curing the drug addiction conditions in a better way and eliminate unnecessary use of medicines.

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