ALDH2 and ADH1B Interactions in Retrospective Reports of Low-Dose Reactions and Initial Sensitivity to Alcohol in Asian American College Students

Abstract

Background A mechanistic model has been proposed for how alcohol metabolizing gene variants protect individuals from the development of alcohol use disorders, with heightened sensitivity to alcohol being an early step (endophenotype) in this model. The present study was designed to determine whether possession of two alcohol metabolizing genes variations, the aldehyde dehydrogenase ALDH2*2 allele and the alcohol dehydrogenase ADH1B*2 allele, was associated with self-reported sensitivity to alcohol at low doses and at initial use. Methods Asian-American college students (N = 784) of Chinese and Korean descent were genotyped at the ALDH2 and ADH1B loci and assessed for lifetime alcohol symptoms following one or two drinks and level of response to alcohol during the first five lifetime drinking episodes. Results Participants who had an ALDH2*2 allele were more likely to report experiencing all six low-dose symptoms and having heightened initial response to alcohol. An interaction was found between ALDH2*2 and ADH1B*2, with ADH1B*2 being associated with heightened self-reported sensitivity to alcohol only in individuals who also possessed one ALDH2*2 allele. Conclusions These findings suggest the effects of ADH1B*2 may be felt more strongly in Asians who already have some heightened sensitivity to alcohol from possessing one ALDH2*2 allele, but who are not too sensitized to alcohol from possessing two ALDH2*2 alleles. These results offer additional insight into the discrepant findings that have been reported in the literature for the role of ADH1B*2 in response to alcohol and the development of alcohol-related problems.

ALDH2*2 and peer drinking in East Asian college students

“…About 44% of subjects reported that most or all of their friends got drunk. Because ALDH2 *2/*2 carriers are more sensitive to alcohol (31,32), differences between ALDH2 *2/*2 and ALDH2 *1/*2 were also evaluated. The two genotypes were similar ( p > .05) on all study variables, including alcohol consumption, t ( 97 ) = − 1.04, p = .300, and number of friends who got drunk, χ 2 (4, 100) = 1.81, p = .771.…”

“…For example, while ALDH2 *2(−) carriers may be more susceptible to the permissive norms for drinking associated with higher levels of peer drunkenness in college settings, ALDH2 *2(+) carriers may be less so because of the negative consequences of drunken behavior, which can include students vomiting or passing out in public places (28). ADLH2 *2(+) carriers may be more deterred by these instances, as the protective effects of ALHD2 *2(+) in reducing drinking include such adverse reactions as nausea and drowsiness that can, for some individuals, occur after only 1 to 2 drinks (31,32). Seemingly in support of this, Hendershot et al (38) found that carriers of ALDH2 *2(+) report higher negative alcohol expectancies and physiological expectancies such as dizziness and nausea compared to carriers of ADLH2 *2(−).…”

“…The low frequency of ALDH2 *2/*2 ( n = 11) precluded us from analyzing differences across genotypes. Individuals with ALDH2 *2/*2 can experience a more intense alcohol-related flushing response (31,32), which may deter them more from consuming alcohol than ALHD2 *1/*2 carriers. Although in the current sample, students with ALDH2 *2/*2 and ALDH2 *1/*2 reported similar amounts of ethanol consumed and numbers of peers who got drunk.…”

Endophenotypes for Alcohol Use Disorder: An Update on the Field

“…A systematic genome-wide scan in the same Native American sample identified regions of interest on chromosomes 6, 10, 12, and 17 that were associated with participants’ self-reported subjective LR early in their drinking careers [53]. Variation in the aldehyde dehydrogenase gene (ALDH2) on chromosome 12 was associated with self-reported subjective LR early in the drinking careers of a sample of Chinese- and Korean-American college students [54]. Finally, variants in the cholinergic nicotinic receptor gene cluster ( CHRNA5-CHRNA3-CHRNB4) on chromosome 15 [55, 56] and genes sets implicated in neuronal signaling [57] were associated with LR in a sample of young adult offspring of alcoholics.…”

A Brief History of Research on the Genetics of Alcohol and Other Drug Use Disorders

“…The protective effects for AUDs (but not SUDs) from some variations in genes that produce the major alcohol-metabolizing enzymes have long been known Eng et al, 2007;Hubacek et al, 2012;Li et al, 2011;Luczak et al, 2011). One example is a mutation seen in about 40% of Asians in the gene producing the enzyme aldehyde dehydrogenase (ALDH) that is responsible for the metabolism of the fi rst breakdown product of alcohol, acetaldehyde.…”