Article

Protective Association of Genetic Variation in Alcohol Dehydrogenase With Alcohol Dependence in Native American Mission Indians

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States
American Journal of Psychiatry (Impact Factor: 13.56). 02/2003; 160(1):41-6. DOI: 10.1176/appi.ajp.160.1.41
Source: PubMed

ABSTRACT Two alcohol dehydrogenase genes (ADH2 and ADH3 on chromosome 4) and one aldehyde dehydrogenase gene (ALDH2 on chromosome 12) exhibit functional polymorphisms. The goal of this study was to determine whether any associations exist between the ADH2, ADH3, and ALDH2 polymorphisms and alcohol dependence in a group of Native Americans. An additional goal was to determine if any associations exist between these polymorphisms and the endophenotype, maximum number of drinks ever consumed in a 24-hour period.
Mission Indian adults (N=340) were recruited for participation from reservations in southern California. Each participant completed an interview with the Semi-Structured Assessment for the Genetics of Alcoholism. A blood sample was collected from each participant for genotyping at the ALDH2, ADH2, and ADH3 loci.
Sixty percent of all participants (72% of men and 53% of women) met lifetime DSM-III-R criteria for alcohol dependence. A significant difference in the ADH2 allele distributions was found between alcohol-dependent and non-alcohol-dependent participants. Those with alcohol dependence were significantly less likely to have the ADH2*3 allele (odds ratio=0.28) and significantly more likely to have the ADH2*1 allele (odds ratio=2.00) than those who were not alcohol dependent. Individuals with ADH2*3 reported a lower number of maximum drinks ever consumed in a 24-hour period, compared to those without this allele.
These results are consistent with genetic linkage studies showing protective associations for alcohol dependence and related behavior on chromosome 4 and suggest that ADH2 polymorphisms may account for these findings. These results also highlight the utility of evaluating protective factors in populations with high rates of alcohol dependence.

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    • "The present report is part of a larger family study exploring risk factors for substance dependence in a community sample of American Indians (Ehlers et al., 2001a,b,c,d, 2004a, 2008c; Gilder et al., 2004, 2006, 2007, 2009). The lifetime prevalence of trauma and substance dependence in this Indian population is high and genetic and environmental risk factors for substance dependence have been identified (Ehlers and Wilhelmsen, 2005, 2007; Ehlers et al., 2004b, 2006, 2007a,b,c, 2008a,b, 2009, 2010a,b, 2011, 2012; Gizer et al., 2011; Wall et al., 2003; Wilhelmsen and Ehlers, 2005). However, a description of the potential effects of current trauma, substance dependence and other mental health issues on thoughts of historical loss and associated symptomatology has not been reported in this Indian population. "
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    ABSTRACT: The American Indian experience of historical trauma is thought of as both a source of intergenerational trauma responses as well as a potential causative factor for long-term distress and substance abuse among communities. The aims of the present study were to evaluate the extent to which the frequency of thoughts of historical loss and associated symptoms are influenced by: current traumatic events, post traumatic stress disorder (PTSD), cultural identification, percent Native American Heritage, substance dependence, affective/anxiety disorders, and conduct disorder/antisocial personality disorder (ASPD). Participants were American Indians recruited from reservations that were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), The Historical Loss Scale and The Historical Loss Associated Symptoms Scale (to quantify frequency of thoughts and symptoms of historical loss) the Stressful-Life-Events Scale (to assess experiences of trauma) and the Orthogonal Cultural Identification Scale (OCIS). Three hundred and six (306) American Indian adults participated in the study. Over half of them indicated that they thought about historical losses at least occasionally, and that it caused them distress. Logistic regression revealed that significant increases in how often a person thought about historical losses were associated with: not being married, high degrees of Native Heritage, and high cultural identification. Additionally, anxiety/affective disorders and substance dependence were correlated with historical loss associated symptoms. In this American Indian community, thoughts about historical losses and their associated symptomatology are common and the presence of these thoughts are associated with Native American Heritage, cultural identification, and substance dependence.
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    • "The present report is part of a larger study exploring risk factors for substance dependence among Native American Indians (see Ehlers et al., 2001a,b,c,d; 2004a, 2008c; Gilder et al., 2004, 2006, 2007, 2009). The lifetime prevalence of substance dependence in this Indian population is high and evidence for heritability and linkage to specific chromosome locations and associations with candidate genes have been demonstrated (see Ehlers and Wilhelmsen, 2005, 2007; Ehlers et al., 2004b, 2006b, 2007a,b,c, 2008a,b, 2009a,b, 2010a,b; Wall et al., 2003; Wilhelmsen and Ehlers, 2005). The current study's aims were to: (1) map loci linked to STIM phenotypes and (2) to determine if there was overlap of the loci identified for STIM phenotypes and loci previously mapped for alcohol and other substance dependence in this American Indian community. "
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    • "Both of the SNPs associated with withdrawal symptoms have shown previous evidence of association with alcohol dependence and related phenotypes. Specifically, rs2066702, which has been described in the literature as identifying the ADH1B*3 allele, has been associated with alcohol dependence in samples of African descent (Edenberg et al., 2006; Ehlers et al., 2001a, 2007; Luo et al., 2006) and an earlier study of this Native American population that used a subset of the participants described in the present study (Wall et al., 2003). Similarly, rs3762894 has been associated with alcohol dependence in several recent studies of ADH4 polymorphisms (Edenberg et al., 2006; MacGregor et al., 2009). "
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