The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men

Konishi, Tamiko; Calvillo, Maria; Leng, A.i-She; Feng, Jack; Lee, Tong; Lee, Hansen; Smith, James; Sial, Shahid H.; Berman, Nancy; French, Samuel W.; Eysselein, Viktor E.; Lin, Keh‐Ming; Wan, Yvonne

doi:10.1016/s0014-4800(03)00006-6

Cited by 65 publications

(41 citation statements)

References 39 publications

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“…Studies evaluating the association between CYP2E1 polymorphism and alcohol dependence in different races have provided contradictory results. Some studies found the CYP2E1*c2 allele as a risk factor for alcoholism (18,33,39), while others did not detect this relationship (38,40). Our study did not find differences in CYP2E1 allele or genotype distribution between alcoholdependent subjects and controls.…”

Section: Discussioncontrasting

confidence: 70%

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men

Cichoż‐Lach

Celiński

Wojcierowski

et al. 2010

Braz J Med Biol Res

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Section: Discussioncontrasting

confidence: 70%

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men

Cichoż‐Lach

Celiński

Wojcierowski

et al. 2010

Braz J Med Biol Res

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“…There are no reports of impaired CYP2E1 expression or activity or polymorphisms in humans other than synonymous single nucleotide polymorphisms and differ among ethnic populations (100)(101)(102). CYP2E1 is believed to play an important role in alcohol-induced liver injury associated with oxidative stress, mitochondrial damage and glutathione depletion (22,103), and alcohol-induced liver disease (104,105).…”

Section: Cyp2e1-humanized Micementioning

confidence: 99%

Cytochrome P450 and Xenobiotic Receptor Humanized Mice

Gonzalez

2006

Annu. Rev. Pharmacol. Toxicol.

144

107

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Most xenobiotics that enter the body are subjected to metabolism that functions primarily to facilitate their elimination. Metabolism of certain xenobiotics can also result in the production of electrophilic derivatives that can cause cell toxicity and transformation. Many xenobiotics can also activate receptors that in turn induce the expression of genes encoding xenobiotic-metabolizing enzymes and xenobiotic transporters. However, there are marked species differences in the way mammals respond to xenobiotics, which are due in large part to molecular differences in receptors and xenobioticmetabolizing enzymes. This presents a problem in extrapolating data obtained with rodent model systems to humans. There are also polymorphisms in xenobiotic-metabolizing enzymes that can impact drug therapy and cancer susceptibility. In an effort to generate more reliable in vivo systems to study and predict human response to xenobiotics, humanized mice are under development.

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“…Although classical genetic studies, such as twin and adoption studies, estimated the genetic contribution to alcoholism as approximately 0.5, 1-3 few family-based linkage studies have yielded consistent linkages at specific loci. [4][5][6][7] The genetic polymorphisms in the alcohol metabolizing pathway, such as aldehyde dehydrogenase 2 (ALDH2) 8 and alcohol dehydrogenase (ADH) [9][10][11][12] appear to be associated with alcoholism vulnerability. Aside from the genes encoding the metabolizing enzyme, there appear to be no single gene that plays a significant role in alcoholism, and small functional gene effects may act in conjunction with environmental factors to promote alcoholism.…”

Section: Introductionmentioning

confidence: 99%

Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans

et al. 2006

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We tested if cannabinoid type 2 receptor (CB2) in the central nervous system plays a role in alcohol abuse/dependence in animal model and then examined an association between the CB2 gene polymorphism and alcoholism in human. Mice experiencing more alcohol preference by drinking showed reduced Cb2 gene expression, whereas mice with little preference showed no changes of it in ventral midbrain. Alcohol preference in conjunction with chronic mild stress were enhanced in mice treated with CB2 agonist JWH015 when subjected to chronic stress, whereas antagonist AM630 prevented development of alcohol preference. There is an association between the Q63R polymorphism of the CB2 gene and alcoholism in a Japanese population (P ¼ 0.007; odds ratio 1.25, 95% CI, (1.06-1.47)). CB2 under such environment is associated with the physiologic effects of alcohol and CB2 antagonists may have potential as therapies for alcoholism.

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The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men

Cited by 65 publications

References 39 publications

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men

Cytochrome P450 and Xenobiotic Receptor Humanized Mice

Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans

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