MAOA Interacts With the ALDH2 Gene in Anxiety-Depression Alcohol Dependence

Background: Alcohol dependence is usually comorbid with anxiety disorder, depressive disorder, or both; this comorbidity may increase drinking behavior. We previously hypothesized that anxiety–depressive alcohol dependence (ANX/DEP ALC) was a genetically specific subtype of alcohol dependence. ANX/DEP ALC may be related to dopamine and serotonin, which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The aim of this study was to determine whether the interaction between the MAOA and the ALDH2 genes is associated with ANX/DEP ALC. Methods: We recruited 383 Han Chinese men in Taiwan: 143 ANX/DEP ALC and 240 healthy controls. The diagnosis of ANX/DEP ALC (alcohol dependence with a past or current history of anxiety, depressive disorder, or both) was made using DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR (variable number of tandem repeat located upstream) were determined using PCR-RFLP. Results: The ALDH2, but not the MAOA-uVNTR, polymorphism was associated with ANX/DEP ALC. After stratifying the MAOA-uVNTR polymorphism, we found a stronger association between the ALDH2*1/*2 and *2/*2 genotypes and the controls in the MAOA-uVNTR 4-repeat subgroup. Logistic regression significantly associated the interaction between ALDH2 and MAOA variants with ANX/DEP ALC. Conclusion: We conclude that the MAOA and ALDH2 genes interact in ANX/DEP ALC. Although the MAOA gene alone is not associated with ANX/DEP ALC, we hypothesize that different variants of MAOA-uVNTR polymorphisms modify the protective effects of the ALDH2*2 allele on ANX/DEP ALC in Han Chinese in Taiwan.