Genetic variation in alcoholism and opioid addiction susceptibility and treatment: a pharmacogenomic approach

Catherine Demery-Poulos; Joseph M. Chambers; Catherine Demery-Poulos; Joseph M. Chambers

doi:10.3934/molsci.2021016

AIMS Molecular Science

2021, Volume 8, Issue 4: 202-222. doi: 10.3934/molsci.2021016

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Review

Genetic variation in alcoholism and opioid addiction susceptibility and treatment: a pharmacogenomic approach

Department of Pharmaceutical Sciences, College of Pharmacy, Natural and Health Sciences, Manchester University, Fort Wayne, Indiana, United States

Received: 12 July 2021 Accepted: 29 September 2021 Published: 09 October 2021

Alcohol and opioid abuse have pervasive and detrimental consequences from the individual to societal level. The extent of genetic contribution to alcoholism has been studied for decades, yielding speculative and often inconsistent results since the previous discovery of two pharmacokinetic variants strongly protective against alcoholism. The neurobiology of addiction involves innumerate genes with combinatorial and epistatic interactions, creating a difficult landscape for concrete conclusions. In contrast, pharmacogenomic variation in the treatment of alcoholism yields more immediate clinical utility, while also emphasizing pathways crucial to the progression of addiction. An improved understanding of genetic predisposition to alcohol abuse has inherent significance for opioid addiction and treatment, as the two drugs induce the same reward pathway. This review outlines current knowledge, treatments, and research regarding genetic predisposition to alcoholism, focusing on pharmacodynamic variation within the dopaminergic system and shared implications for opioid abuse. Multifaceted and highly polygenic, the phenotype of addiction seems to grow more complex as new research extends the scope of its impact on the brain, body, and progeny.
- pharmacogenomics,
- alcoholism,
- opioid,
- addiction,
- genetics,
- alcohol,
- pharmacodynamics,
- pharmacokinetics,
- substance abuse
Citation: Catherine Demery-Poulos, Joseph M. Chambers. Genetic variation in alcoholism and opioid addiction susceptibility and treatment: a pharmacogenomic approach[J]. AIMS Molecular Science, 2021, 8(4): 202-222. doi: 10.3934/molsci.2021016

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Abstract

Alcohol and opioid abuse have pervasive and detrimental consequences from the individual to societal level. The extent of genetic contribution to alcoholism has been studied for decades, yielding speculative and often inconsistent results since the previous discovery of two pharmacokinetic variants strongly protective against alcoholism. The neurobiology of addiction involves innumerate genes with combinatorial and epistatic interactions, creating a difficult landscape for concrete conclusions. In contrast, pharmacogenomic variation in the treatment of alcoholism yields more immediate clinical utility, while also emphasizing pathways crucial to the progression of addiction. An improved understanding of genetic predisposition to alcohol abuse has inherent significance for opioid addiction and treatment, as the two drugs induce the same reward pathway. This review outlines current knowledge, treatments, and research regarding genetic predisposition to alcoholism, focusing on pharmacodynamic variation within the dopaminergic system and shared implications for opioid abuse. Multifaceted and highly polygenic, the phenotype of addiction seems to grow more complex as new research extends the scope of its impact on the brain, body, and progeny.

Abbreviations

ADH1B

alcohol dehydrogenase 1B

ADH1C

alcohol dehydrogenase 1C

ALDH2

aldehyde dehydrogenase 2

AUD

alcohol use disorder

AUDIT-C

Alcohol Use Disorder Identification Test – Consumption

Ca-AOTA

calcium-bis (N-acetylhomotaurinate)

CYP2E1

cytochrome P450 family 2, subfamily e, polypeptide 1

DMC

differentially-methylated cytosine

DRD2

dopamine receptor D2

FAM107B

family with sequence similarity 107 member B

FICD

FIC domain protein adenylyltransferase

FTO

fat, mass, and obesity-associated gene

FUT2

fucosyltransferase 2

GABA

gamma aminobutyric acid

GCKR

glucokinase receptor

GPCR

G-protein coupled receptor

GWAS

genome-wide association study

K_Ca

calcium-activated potassium channel

KCNB1 (K_V2.1)

potassium voltage-gated channel subfamily B member 1

KCNMA1 (K_Ca1.1)

potassium calcium-activated channel subfamily M alpha 1

KCNQ5 (K_V7.5)

potassium voltage-gated channel subfamily Q member 5

K_IR

inwardly-rectifying potassium channel

KIF2

kinesin family member 2A

KLB

klotho beta

KOR

kappa opioid receptor

K_V

voltage-dependent potassium channel

LOC257642

rRNA promoter binding protein

MAD2L2

mitotic arrest deficient 2 like 2

NAc

nucleus accumbens

NDMA

N-methyl-D-aspartate

OPRM1

µ opioid receptor 1

ORC4

origin recognition complex subunit 4

PDE4B

cAMP-specific 3′,5′-cyclic phosphodiesterase 4B

PFC

prefrontal cortex

PPAP2B

phosphatidate phosphohydrolase type 2b

PTPRM

protein tyrosine phosphatase receptor type M

RDS

Reward Deficiency Syndrome

RNF165

ring finger protein 165

SIX3

SIX homeobox 3

SLC39A8

solute carrier family 39 member 8

SLC39A13

solute carrier family 39 member 13

VTA

ventral tegmental area

WBSCR17

polypeptide N-acetylgalactosaminyltransferase 17

Conflict of interest

The authors declare no conflict of interest in this paper.

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