The interaction of reward genes with environmental factors in contribution to alcoholism in mexican americans.
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 < or =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 < or =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.
Du
Yanlei
Y
Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
Wan
Yu-Jui Yvonne
YJ
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D004493:Education; D005260:Female; D005838:Genotype; D006801:Humans; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012201:Reward; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012931:Social Environment; D012959:Socioeconomic Factors; D011795:Surveys and Questionnaires; D055815:Young Adult
C485764:OPRM1 protein, human; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins