Association of ALDH1 Promoter Polymorphisms With Alcohol‐Related Phenotypes in Southwest California Indians

Ehlers, Cindy L.; Spence, John P.; Wall, Tamara L.; Gilder, David A.; Carr, Lucinda G.

doi:10.1097/01.alc.0000141821.06062.20

Cited by 53 publications

(49 citation statements)

References 29 publications

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“…67 Moreover, a recent study has shown association between ALDH1 promoter polymorphisms and alcohol-related phenotypes in southwest California Indians. 120 Moreover, there is evidence of decreases in ALDH1 levels in post-mortem brains of persons with , and body weight in adult, male P rats (n ¼ 6-8/group). Lisinopril only affected the EtOH intake (top panel).…”

Section: Alcohol Metabolismmentioning

confidence: 98%

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Bertsch

Strother

et al. 2006

Pharmacogenomics J

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We describe a comprehensive translational approach for identifying candidate genes for alcoholism. The approach relies on the cross-matching of animal model brain gene expression data with human genetic linkage data, as well as human tissue data and biological roles data, an approach termed convergent functional genomics. An analysis of three animal model paradigms, based on inbred alcohol-preferring (iP) and alcohol-non-preferring (iNP) rats, and their response to treatments with alcohol, was used. A comprehensive analysis of microarray gene expression data from five key brain regions (frontal cortex, amygdala, caudate-putamen, nucleus accumbens and hippocampus) was carried out. The Bayesian-like integration of multiple independent lines of evidence, each by itself lacking sufficient discriminatory power, led to the identification of high probability candidate genes, pathways and mechanisms for alcoholism. These data reveal that alcohol has pleiotropic effects on multiple systems, which may explain the diverse neuropsychiatric and medical pathology in alcoholism. Some of the pathways identified suggest avenues for pharmacotherapy of alcoholism with existing agents, such as angiotensin-converting enzyme (ACE) inhibitors. Experiments we carried out in alcohol-preferring rats with an ACE inhibitor show a marked modulation of alcohol intake. Other pathways are new potential targets for drug development. The emergent overall picture is that physical and physiological robustness may permit alcohol-preferring individuals to withstand the aversive effects of alcohol. In conjunction with a higher reactivity to its rewarding effects, they may able to ingest enough of this nonspecific drug for a strong hedonic and addictive effect to occur.

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Section: Alcohol Metabolismmentioning

confidence: 98%

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Bertsch

Strother

et al. 2006

Pharmacogenomics J

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“…Other than the ALDH2 Ã 2 allele, the genetic influence of ALDHs on the risk for alcohol dependence appears, if present, to be modest. Protective roles against alcohol dependence have been suggested for the ALDH1A1 Ã 2 allele in Southwest California Indians [108] and for the ALDH1A1 Ã 3 allele in African Americans [106].…”

Section: Aldehyde Dehydrogenasementioning

confidence: 99%

New findings on the genetic influences on alcohol use and dependence

Higuchi

Matsushita

Kashima

2006

Current Opinion in Psychiatry

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Despite great advances in understanding of genetic vulnerability in alcohol use disorders, only two gene complexes, ADH and ALDH2, have been identified as having defined effects on alcohol use and liability to dependence in humans. New genes associated with increased risks for the disorder will certainly be added to this list in the near future. Neurobiological analyses of the effects of these genes will surely contribute to further understanding of the cause of alcohol dependence and the interindividual differences in risks.

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“…The impact of functional variation in ADH1B and ALDH2 genes on alcohol metabolism have been fairly well characterized; however, there are large interindividual differences in alcohol elimination rates that still remain unexplained. Of potential signi fi cance in this regard may be polymorphisms in ADH4 [ 90,91 ] , ADH7 [ 39,69 ] , and ALDH1A1 [ 92,93 ] as well as the promoter regions of ALDH2 [ 94 ] . Further studies are needed to evaluate the in fl uence of these polymorphisms on the activity of ADH and ALDH and on alcohol levels and elimination rates in individuals, as well as on the physiological response to alcohol consumption and alcoholism.…”

Section: Discussionmentioning

confidence: 99%

Genetics of Alcohol Metabolism

Ramchandani

2012

Alcohol, Nutrition, and Health Consequences

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Key PointsAlcohol metabolism occurs mainly via hepatic oxidation and is governed by the catalytic properties • of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH2). Genetic polymorphisms in • ADH1B and ALDH2 , and ethnic differences in the prevalence of these polymorphisms, result in increased variation in alcohol metabolism among individuals. Polymorphisms in • ADH1B result in variants that code for isozymes that tend to show a faster rate of alcohol metabolism, while the ALDH2*2 polymorphism results in a "de fi cient" form of ALDH2 that causes an accumulation of acetaldehyde and its associated physiological effects.• ADH and ALDH polymorphisms are also associated with a protective effect on the development of alcoholism. The allele frequencies of ADH1B*2 , ADH1B*3 , and ALDH2*2 are signi fi cantly lower in individuals diagnosed with alcohol dependence compared to controls. Further evaluation of the factors, both genetic and environmental, regulating the rates of alcohol • and acetaldehyde metabolism, will help improve our understanding of the metabolic basis and consequences of alcohol's effects, including the risk and consequences of alcohol-related organ damage, developmental problems, as well as alcohol dependence.

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Association of ALDH1 Promoter Polymorphisms With Alcohol‐Related Phenotypes in Southwest California Indians

Abstract: Results from this study suggest that ALDH1A1*2 may be associated with protection from the development of alcohol and other substance use disorders.

Cited by 53 publications

References 29 publications

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

New findings on the genetic influences on alcohol use and dependence

Genetics of Alcohol Metabolism

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