The Interaction of Reward Genes With Environmental Factors in Contribution to Alcoholism in Mexican Americans

Abstract

Background Alcoholism is a polygenic disorder resulting from reward deficiency; polymorphisms in reward genes including serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR), A118G in opioid receptor mu1 (OPRM1), and −141C Insertion/Deletion (Ins/Del) in dopamine receptor D2 (DRD2) as well as environmental factors (education and marital status) might affect the risk of alcoholism. Objective of the current study was to examine the main and interacting effect of these 3 polymorphisms and 2 environmental factors in contribution to alcoholism in Mexican Americans. Methods Genotyping of 5-HTTLPR, OPRM1 A118G, and DRD2−141C Ins/Del was performed in 365 alcoholics and 338 nonalcoholic controls of Mexican Americans who were gender-and age-matched. Alcoholics were stratified according to tertiles of MAXDRINKS, which denotes the largest number of drinks consumed in one 24-hour period. Data analysis was done in the entire data set and in each alcoholic stratum. Multinomial logistic regression was conducted to explore the main effect of 3 polymorphisms and 2 environmental factors (education and marital status); classification tree, generalized multifactor dimensionality reduction (GMDR) analysis, and polymorphism interaction analysis version 2.0 (PIA 2) program were used to study factor interaction. Results Main effect of education, OPRM1, and DRD2 was detected in alcoholic stratum of moderate and/or largest MAXDRINKS with education ≤12 years, OPRM1 118 A/A, and DRD2 −141C Ins/Ins being risk factors. Classification tree analysis, GMDR analysis, and PIA 2 program all supported education*OPRM1 interaction in alcoholics of largest MAXDRINKS with education ≤12 years coupled with OPRM1 A/A being a high risk factor; dendrogram showed synergistic interaction between these 2 factors; dosage-effect response was also observed for education*OPRM1 interaction. No definite effect of marital status and 5-HTTLPR in pathogenesis of alcoholism was observed. Conclusions Our results suggest main effect of education background, OPRM1 A118G, and DRD2 −141C Ins/Del as well as education*OPRM1 interaction in contribution to moderate and/or severe alcoholism in Mexican Americans. Functional relevance of these findings still needs to be explored.

Interrelationship between family history of alcoholism and generational status in the prediction of alcohol dependence in US Hispanics

“…Studies of gene-environment interactions using measured genes in Hispanic populations are very limited. One study, in a sample of Mexican Americans, showed that having less than or equal to 12 years of education paired with a risk genotype at OPRM1—a Mu opioid receptor gene—was associated with increased heavy drinking (Du and Wan, 2009). …”

The Association Between the SLC6A3 VNTR 9-Repeat Allele and Alcoholism-A Meta-Analysis

“…The dopaminergic neurotransmission pathway is a pivotal part of the reward system, and some components including dopamine receptor D2 ( DRD2 ) (Blum et al, 1990; Du and Wan, 2009; Noble, 2003; Wang et al, 2007) have been associated with alcoholism. SLC6A3 protein is located at the pre-synaptic membrane of the dopaminergic synapse.…”

Impact of A118G Polymorphism on the Mu Opioid Receptor Function in Pain

“…So, the authors suggest that A118G SNP can be associated to a protective effect against chronic pain [37]. Carrying the G allele has been previously correlated with a protecting function against respiratory depressive effects [34], opioid dependence [4] and alcoholism [38,39]. In opposition, several reports failed to find the same correlations [35,[40][41][42].…”