Association of Superoxide Dismutase 2 (SOD2) Genotype with Gray Matter Volume Shrinkage in Chronic Alcohol Users: Replication and Further Evaluation of an Addiction Gene Panel

Abstract

Background:Reduction in brain volume, especially gray matter volume, has been shown to be one of the many deleterious effects of prolonged alcohol consumption. High variance in the degree of gray matter tissue shrinkage among alcohol-dependent individuals and a previous neuroimaging genetics report suggest the involvement of environmental and/or genetic factors, such as superoxide dismutase 2 (SOD2). Identification of such underlying factors will help in the clinical management of alcohol dependence.Methods:We analyzed quantitative magnetic resonance imaging and genotype data from 103 alcohol users, including both light drinkers and treatment-seeking alcohol-dependent individuals. Genotyping was performed using a custom gene array that included genes selected from 8 pathways relevant to chronic alcohol-related brain volume loss.Results:We replicated a significant association of a functional SOD2 single nucleotide polymorphism with normalized gray matter volume, which had been reported previously in an independent smaller sample of alcohol-dependent individuals. The SOD2-related genetic protection was observed only at the cohort’s lower drinking range. Additional associations between normalized gray matter volume and other candidate genes such as alcohol dehydrogenase gene cluster (ADH), GCLC, NOS3, and SYT1 were observed across the entire sample but did not survive corrections for multiple comparisons.Conclusion:Converging independent evidence for a SOD2 gene association with gray matter volume shrinkage in chronic alcohol users suggests that SOD2 genetic variants predict differential brain volume loss mediated by free radicals. This study also provides the first catalog of genetic variations relevant to gray matter loss in chronic alcohol users. The identified gene-brain structure relationships are functionally pertinent and merit replication.

The Disease Model of Addiction: The Impact of Genetic Variability in the Oxidative Stress and Inflammation Pathways on Alcohol Dependance and Comorbid Psychosymptomatology

“…The shrinking of the brain volume subsequently causes cognitive function deficits in executive and occupational functioning, attention, working, and long-term memory, as well as the poor performance of daily living activities, social skills, and problem-solving in alcohol-addicted patients [44]. The brain is extremely vulnerable to oxidative stress, caused by the reduced concentration of antioxidant enzymes and increased oxygen metabolism [45]. Oxidative stress can damage brain white matter and lead to cognitive function impairment [46].…”

Relapse risk revealed by degree centrality and cluster analysis in heroin addicts undergoing methadone maintenance treatment

“…From the view of neurodevelopment, the large-scale changed DC in hubs of high relapse risk network pattern could be interpreted as the consequence of complex interactions between genetic, epigenetic and environmental factors. Genetic factor accounts for approximately half of the risk for addiction (Volkow & Li, 2005), and a series of gene variants are associated with addiction vulnerability by impacting on synaptic plasticity (Oliver et al, 2018; Randesi et al, 2018), receptor binding affinity (Shi et al, 2002), dopamine receptor density (Noble, 2000), neuron cell sensitivity to the substance of abuse (Alia-Klein et al, 2011), cortical neurotransmission and neurogenesis (Crews & Vetreno, 2011), and gray matter volume shrinkage in chronic substance use (Gitik et al, 2016). In addition, the epigenetic factors also contribute to the risk for addiction.…”

“…Genetic factor accounts for approximately half of the risk for addiction (Volkow & Li, 2005), and a series of gene variants are associated with addiction vulnerability by impacting on synaptic plasticity (Oliver et al, 2018;Randesi et al, 2018), receptor binding affinity Note: HC, healthy control; HD, patients diagnosed with heroin dependence; S1, subgroup-1; S2, subgroup-2; NA, not applicable; S.D., standard deviation; *, statistically significant; HD-HC, HD v. HC, and so on. (Shi et al, 2002), dopamine receptor density (Noble, 2000), neuron cell sensitivity to the substance of abuse (Alia-Klein et al, 2011), cortical neurotransmission and neurogenesis (Crews & Vetreno, 2011), and gray matter volume shrinkage in chronic substance use (Gitik et al, 2016). In addition, the epigenetic factors also contribute to the risk for addiction.…”

Customized DNA–directed precision nutrition to balance the brain reward circuitry and reduce addictive behaviors

“…These differences result from genetic differences: that is, polymorphisms in genotypes and their gene expressions. An example of this is that alcohol affects Asians and Native Americans quite differently than Caucasians, and that the alcohol dehydrogenase gene polymorphism has predictive value in alcohol addiction [14]. Genotypes represent specific gene variants.…”