Genetic differences in alcohol sensitivity and the 
inheritance of alcoholism risk

Heath, Andrew C.; Madden, Peter; Bucholz, K. K.; Dinwiddie, Stephen H.; Slutske, W. S.; Bierut, Laura J.; Rohrbaugh, John; Statham, D. J.; Dunne, Michael P.; Whitfield, John B.; Martin, Nicholas G.

doi:10.1017/s0033291799008909

Cited by 261 publications

(218 citation statements)

References 46 publications

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“…A similar finding was obtained by observation of very rapid drinking results in an oral alcohol challenge protocol, although at later time points with falling BACs, the FHP subjects tended to demonstrate lower LRs than the FHNs . Second, supporting the probable reliability and validity of a low LR are data from all four relevant longitudinal studies showing that this phenotype predicts future heavier drinking and alcohol-related problems, with data generated in the United States, Australia, and Denmark (Heath et al, 1999;Rodriguez et al, 1993;Smith, 1996, 2000;Volavka et al, 1996). When used as part of an alcohol challenge protocol, the LR measures appear reliable as the correlation between two different doses of alcohol over several weeks is as high at .70, with a test-retest correlation at the same dose as high as .60 (Schuckit and Gold, 1988;Schuckit, 1985;Viken et al, 2003).…”

Section: Introductionmentioning

confidence: 78%

The level of response to alcohol in daughters of alcoholics and controls

Eng

Schuckit

Smith

2005

Drug and Alcohol Dependence

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Background: The low level of response (LR) to alcohol is a genetically influenced characteristic related to the development of alcohol use disorders (AUDs). This phenotype is found in men with a family history (FH) of alcoholism, predicts future AUDs, and has heritabilities as high as 60%. However, despite evidence of genetic influences for AUDs in both sexes, the majority of studies evaluating differences in LR across high-and low-risk groups have been conducted on males, and it is unclear how generalizable these results are to women. Methods: Twenty-five women who are family history positive (FHP) for alcohol dependence were matched with 25 women with no FH of alcoholism (FHN) on factors that may impact LR. Using an alcohol challenge paradigm, data on the reaction to a moderate dose of alcohol were gathered over a period of 3.5 h. Assessments included breath alcohol concentrations (BrACs), the Subjective High Assessment Scale (SHAS), as well as body sway or static ataxia. Results: Family history positives reported lower subjective intoxication than FHNs. In addition, when body sway scores were corrected for skewness, FHPs had significantly lower scores on alcohol-related changes in lateral sway. These differences remained after considering the effects of drinking history and BrAC values. Conclusions: This study evaluated the LR to alcohol in the largest sample of alcohol challenges in matched FHP and FHN women to date. Overall, the findings are consistent with most data from earlier investigations of smaller sized samples of FHP women. The results suggest that, similar to sons of alcoholics, a low LR to alcohol might also be characteristic of daughters of alcoholics.

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Section: Introductionmentioning

confidence: 78%

The level of response to alcohol in daughters of alcoholics and controls

Eng

Schuckit

Smith

2005

Drug and Alcohol Dependence

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“…Although some studies have found that the ADH1B*2 allele is associated with a lower rate of alcohol dependence (Tanaka et al, 1996;Wall et al, 2005b;Whitfield, 1997), others have not (Luczak et al, 2004;Takeshita et al, 1994). Furthermore, some alcohol challenge studies have found significant associations between ADH1B and level of response to alcohol Duranceaux et al, 2006), but others have not (Heath et al, 1999;Peng et al, 2002). Thus, prior data do not consistently support the hypothesis that ADH1B*2 leads to decreased rates of alcohol dependence via a more intense response to alcohol, and any such relationship may be further obscured when level of response to alcohol is assessed using self-report.…”

Section: Discussionmentioning

confidence: 99%

“…Individuals who are homozygous for ALDH2*2 have been shown to have severe reactions to moderate doses of alcohol, including tachycardia, hypotension, nausea, and vomiting (Wall et al, 1992). Moreover, individuals with the most intense reactions to alcohol may not volunteer for alcohol challenge studies, resulting in participation bias (Heath et al, 1999). …”

mentioning

confidence: 99%

Ethnic Differences in Level of Response to Alcohol Between Chinese Americans and Korean Americans

Duranceaux

Schuckit

Luczak

et al. 2008

J. Stud. Alcohol Drugs

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Objective-Koreans have higher rates of alcohol-use disorders and family history of alcoholism, compared with Chinese. These differences likely reflect both environmental and genetic influences. One genetically influenced characteristic that may contribute to these ethnic differences is level of response to alcohol. Variant alleles of aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH1B) genes are prevalent in individuals of Asian heritage and have been associated with an increased level of response to alcohol and a decreased risk for alcohol dependence. Additionally, a low level of response to alcohol is more common in individuals with a first-degree family history of alcoholism and is predictive of increased risk for this disorder. It also is possible that sociocultural factors have an impact on an individual's response to alcohol. The current study examined self-report level of response to alcohol, ALDH2 and ADH1B, country of origin, and family history of alcoholism in 154 Chinese-and 181 Korean-American college students.Method-Participants were evaluated via in-person interviews and genotyped at the ALDH2 and ADH1B loci.Results-Ethnicity was significantly related to level of response to alcohol, with Koreans having a lower self-reported level of response than Chinese. This relationship remained significant after considering the effects of gender, height, weight, quantity and frequency of alcohol consumption (over the previous 90 days), ALDH2 genotype, ADH1B genotype, country of origin, and first-degree family history of alcohol dependence.

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“…One behavioral characteristic related to this risk is a low level of response to an acute alcohol challenge (Schuckit, 1998), a trait that carries a similar estimated heritability of 40-60% (Schuckit and Smith, 1996;Heath et al, 1999). Linkage studies have identified regions on chromosomes 10, 11, 13, and 20 with LOD scores X3.0 that may contain genes that contribute to the level of response to alcohol (Schuckit et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

Wallace

Newton

Oyasu

et al. 2006

Neuropsychopharmacol

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A low level of response to ethanol is associated with increased risk of alcoholism. A major determinant of the level of response is the capacity to develop acute functional tolerance (AFT) to ethanol during a single drinking session. Mice lacking protein kinase C epsilon (PKCe) show increased signs of ethanol intoxication and reduced ethanol self-administration. Here, we report that AFT to the motorimpairing effects of ethanol is reduced in PKCe (À/À) mice when compared with wild-type littermates. In wild-type mice, in vivo ethanol exposure produced AFT that was accompanied by increased phosphorylation of PKCe and resistance of GABA A receptors to ethanol. In contrast, in PKCe (À/À) mice, GABA A receptor sensitivity to ethanol was unaltered by acute in vivo ethanol exposure. Both PKCe (À/À) and PKCe ( + / + ) mice developed robust chronic tolerance to ethanol, but the presence of chronic tolerance did not change ethanol preference drinking. These findings suggest that ethanol activates a PKCe signaling pathway that contributes to GABA A receptor resistance to ethanol and to AFT. AFT can be genetically dissociated from chronic tolerance, which is not regulated by PKCe and does not alter PKCe modulation of ethanol preference.

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Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk

Abstract: Background. Substantial evidence exists for an important genetic contribution to alcohol dependence risk in women and men. It has been suggested that genetically determined differences in alcohol sensitivity may represent one pathway by which an increase in alcohol dependence risk occurs.

Cited by 261 publications

References 46 publications

The level of response to alcohol in daughters of alcoholics and controls

The level of response to alcohol in daughters of alcoholics and controls

Ethnic Differences in Level of Response to Alcohol Between Chinese Americans and Korean Americans

Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

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