Alcohol-metabolizing genes and alcohol phenotypes in an Israeli household sample.

paper Cited Public

Authors: Meyers, Jacquelyn L; Shmulewitz, Dvora; Aharonovich, Efrat; Waxman, Rachel; Frisch, Amos; Weizman, Abraham; Spivak, Baruch; Edenberg, Howard J; Gelernter, Joel; Hasin, Deborah S
Year: 2013
Journal: Alcoholism, clinical and experimental research
PMID: 23895337
DOI: 10.1111/acer.12176
PMCID: PMC3812252

BACKGROUND: Alcohol dehydrogenase 1B and 1C (ADH1B and ADH1C) variants have been robustly associated with alcohol phenotypes in East Asian populations, but less so in non-Asian populations where prevalence of the most protective ADH1B allele is low (generally <5%). Further, the joint effects of ADH1B and ADH1C on alcohol phenotypes have been unclear. Therefore, we tested the independent and joint effects of ADH1B and ADH1C on alcohol phenotypes in an Israeli sample, with higher prevalence of the most protective ADH1B allele than other non-Asian populations. METHODS: A structured interview assessed lifetime drinking and alcohol use disorders (AUDs) in adult Israeli household residents. Four single nucleotide polymorphisms (SNPs) were genotyped: ADH1B (rs1229984, rs1229982, and rs1159918) and ADH1C (rs698). Regression analysis examined the association between alcohol phenotypes and each SNP (absence vs. presence of the protective allele) as well as rs698/rs1229984 diplotypes (also indicating absence or presence of protective alleles) in lifetime drinkers (n = 1,129). RESULTS: Lack of the ADH1B rs1229984 protective allele was significantly associated with consumption- and AUD-related phenotypes (OR = 1.77 for AUD; OR = 1.83 for risk drinking), while lack of the ADH1C rs698 protective allele was significantly associated with AUD-related phenotypes (OR = 2.32 for AUD). Diplotype analysis indicated that jointly ADH1B and ADH1C significantly influenced AUD-related phenotypes. For example, among those without protective alleles for ADH1B or ADH1C, OR for AUD was 1.87 as compared to those without the protective allele for ADH1B only and was 3.16 as compared to those with protective alleles for both ADH1B and ADH1C. CONCLUSIONS: This study adds support for the relationship of ADH1B and ADH1C and alcohol phenotypes in non-Asians. Further, these findings help clarify the mixed results from previous studies by showing that ADH1B and ADH1C jointly effect AUDs, but not consumption. Studies of the association between alcohol phenotypes and either ADH1B or ADH1C alone may employ an oversimplified model, masking relevant information.

#	Section	Preview
20	Results — Association of individual SNPs and alcohol-related traits	ADH1C-rs698 was significantly associated with alcohol disorder phenotypes; the high risk group had a…
21	Results — Association of ADH1C-rs698/ADH1B-rs1229984 diplotypes and alcohol-related traits	Mean values were significantly different from each other for AD, any AUD, and AD and AUD severity,…
22	Discussion	In this study, we found that variants in two widely studied ADH genes, ADH1B and ADH1C, were…
23	Discussion — ADH1B	Results for associations of ADH1B with AUDs and alcohol consumption are consistent with recent…
24	Discussion — ADH1B	associated with alcohol-related traits (rs1229982) or not associated (rs1159918). The similar allele…
25	Discussion — ADH1C	Association between ADH1C and alcohol phenotypes has been robust in East Asian populations…
26	Discussion — ADH1B and ADH1C	We found that while ADH1B-rs1229984 and ADH1C-rs698 were correlated (r2=0.32; D′=0.44), they did…
27	Discussion — ADH1B and ADH1C	same amount of the variance in these traits (e.g. ∼19% of the variance in AD) as either…
28	Discussion — ADH1B and ADH1C	While prior studies have examined gene-gene interactions between ADH genes (Wu et al., 2012), only…
29	Discussion — ADH1B and ADH1C	Although many gene mapping studies are carried out in Ashkenazi Jewish (AJ) samples (i.e., all four…
30	Discussion — ADH1B and ADH1C	a continuum of genetic ancestry measuring the Northern/Southern European cline, with higher…
31	Discussion — ADH1B and ADH1C	Study limitations are noted. First, we do not claim to have identified all the causative genetic…
32	Discussion — ADH1B and ADH1C	examined two genes in relation to six related alcohol outcomes in an effort to systematically assess…
33	Discussion — ADH1B and ADH1C	In conclusion, this study adds support for the role of ADH1B and ADH1C in alcohol phenotypes in a…

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In this knowledge base

Title	Year	PMID
Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.	2015	24164917
An ADH1B variant and peer drinking in progression to adolescent drinking milestones: evidence of a gene-by-environment interaction.	2014	25257461
The joint effects of ADH1B variants and childhood adversity on alcohol related phenotypes in African-American and European-American women and men.	2014	25410943

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