Genetic alcohol sensitivity regulated by ALDH2 and ADH1B polymorphisms as indicator of mental disorders in Japanese employees.

Aims: Alcohol-related disorders (ARD) have been shown to be accompanied by a variety of other comorbid mental disorders. This study evaluated the associations between a variety of mental disorders and genetic alcohol sensitivity.

Methods: A total of 1944 Japanese workers were interviewed regarding their mental disorders by the Mini-International Neuropsychiatric Interview (M.I.N.I.). We investigated the relationship of ADH1B rs1229984 and ALDH2 rs671 polymorphisms' combination with mental disorder risks. Logistic regression analysis was used to evaluate the associations between those polymorphisms and mental disorders, adjusting for sex, age, and job rank.

Results: The degree of alcohol sensitivity was classified into five groups according to the combination of ADH1B and ALDH2 genotypes (Group I-V in order starting from the lowest alcohol sensitivity). Those with ALDH2 *1/*1 and ADH1B *1/*1 or with ALDH2 *1/*1 and ADH1B *1/*2,*2/*2 (low sensitivity) were significantly or nearly significantly associated with an increased risk of ARD compared with those with ALDH2 *1/*2 and ADH1B *1/*2,*2/*2 as a reference. Those with ALDH2 *1/*1 and ADH1B *1/*1 were also likely to be at an increased risk of any mental disorder except ARD, as well as disorders without comorbid ARD. This tendency was more apparent among women (OR 11.94, 95% CI 0.73-195.63) and non-drinkers (OR 5.43, 95% CI 1.05-28.23).

Conclusion: The genotype combination of ALDH2 *1/*1 and ADH1B *1/*1 is significantly associated with an increased risk of any mental disorder, especially ARD. Non-drinkers or women with ALDH2 *1/*1 and ADH1B *1/*1 are likely to suffer from any mental disorder except ARD.