The Association of ADH and ALDH Gene Variants With Alcohol Drinking Habits and Cardiovascular Disease Risk Factors

Husemoen, Lise Lotte Nystrup; Fenger, Mogens; Friedrich, Nele; Tolstrup, Janne S; Fredriksen, Stine Beenfeldt; Linneberg, Allan

doi:10.1111/j.1530-0277.2008.00780.x

Cited by 54 publications

(57 citation statements)

References 58 publications

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“…A study using crude lysate from HuH7 hepatoma cells reported that mitochondrial ALDH1B1 contributed to the oxidation of short-chain aldehydes including acetaldehyde and propionaldehyde, implying a role for ALDH1B1 in ethanol metabolism (Stewart et al, 1995). In agreement with this report, two recent large population-based studies identified two ALDH1B1 variants that were associated with drinking behavior (A69V) and alcohol-induced hypersensitivity (A86V) in whites (Husemoen et al, 2008;Linneberg et al, 2010). These findings strongly suggest that ALDH1B1 enzyme may be involved in ethanol detoxification and modifications in this enzyme may contribute to alcohol-related diseases.…”

Section: Introductionsupporting

confidence: 79%

“…Although approximately 50% of Asians are carriers of this variant, it is nearly absent in whites. Recent studies have identified the genetic determinants of drinking behavior and alcohol hypersensitivity among whites to be polymorphisms in the human ALDH1B1 gene, which encodes another mitochondrial ALDH isoenzyme (Husemoen et al, 2008;Linneberg et al, 2010). These studies and others (Stewart et al, 1995) are suggestive of a potentially important role of ALDH1B1 in the metabolism of acetaldehyde, but more direct confirmation remains to be established.…”

Section: Discussionmentioning

confidence: 92%

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Aldehyde Dehydrogenase 1B1: Molecular Cloning and Characterization of a Novel Mitochondrial Acetaldehyde-Metabolizing Enzyme

Stagos¹,

Chen²,

Brocker³

et al. 2010

Drug Metab Dispos

121

114

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ABSTRACT:Ethanol-induced damage is largely attributed to its toxic metabolite, acetaldehyde. Clearance of acetaldehyde is achieved by its oxidation, primarily catalyzed by the mitochondrial class II aldehyde dehydrogenase (ALDH2). ALDH1B1 is another mitochondrial aldehyde dehydrogenase (ALDH) that shares 75% peptide sequence homology with ALDH2. Recent population studies in whites suggest a role for ALDH1B1 in ethanol metabolism. However, to date, no formal documentation of the biochemical properties of ALDH1B1 has been forthcoming. In this current study, we cloned and expressed human recombinant ALDH1B1 in Sf9 insect cells. The resultant enzyme was purified by affinity chromatography to homogeneity. The kinetic properties of purified human ALDH1B1 were assessed using a wide range of aldehyde substrates. Human ALDH1B1 had an exclusive preference for NAD ؉ as the cofactor and was catalytically active toward short-and medium-chain aliphatic aldehydes, aromatic aldehydes, and the products of lipid peroxidation, 4-hydroxynonenal and malondialdehyde. Most importantly, human ALDH1B1 exhibited an apparent K m of 55 M for acetaldehyde, making it the second low K m ALDH for metabolism of this substrate. The dehydrogenase activity of ALDH1B1 was sensitive to disulfiram inhibition, a feature also shared with ALDH2. The tissue distribution of ALDH1B1 in C57BL/6J mice and humans was examined by quantitative polymerase chain reaction, Western blotting, and immunohistochemical analysis. The highest expression occurred in the liver, followed by the intestinal tract, implying a potential physiological role for ALDH1B1 in these tissues. The current study is the first report on the expression, purification, and biochemical characterization of human ALDH1B1 protein.

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Section: Introductionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 92%

Aldehyde Dehydrogenase 1B1: Molecular Cloning and Characterization of a Novel Mitochondrial Acetaldehyde-Metabolizing Enzyme

Stagos¹,

Chen²,

Brocker³

et al. 2010

Drug Metab Dispos

121

114

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“…The two main polymorphisms of ADH1C, the Arg272Gln and Ile350Val have an almost complete linkage between each other, as it was expected from previous studies [34]. However, the results regarding the effect of these mutations are not so obvious among Caucasians.…”

Section: Discussionmentioning

confidence: 42%

Combined Effect of ADH1B RS1229984, RS2066702 and ADH1C RS1693482/ RS698 Alleles on Alcoholism and Chronic Liver Diseases

et al. 2011

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Abstract. The aim of this study was to analyze the combined effect of the most frequent alcohol dehydrogenase polymorphisms (Arg48His and Arg370Cys in ADH1B, Arg272Gln and Ile350Val in ADH1C) on the alcohol use habits, alcohol dependence and chronic liver diseases in Hungary. The study included men, aged 45-64 years. Altogether, 241 cases with chronic liver disease (CLD) and 666 randomly selected controls without CLD were analysed for all four polymorphisms. Associations between the polymorphisms, individually, and in combination, and excessive and problem drinking and CLD, were assessed using logistic regression. In this study we have identified a novel mutation, called ADH1B Arg370His. The ADH1C Arg272Gln and Ile350Val showed almost complete linkage. The 272Gln/350Val allele increased the risk of excessive and problem drinking in homozygous form (OR = 1.582, p = 0.035, CI = 1.034-2.421, OR = 1.780, p = 0.016, CI = 1.113-2.848, respectively). The joint analysis showed that when combined with the wild type ADH1C Arg272/Ile350 allele, the ADH1B 48His is protective against CLD (OR = 0.368, p = 0.019, CI = 0.159-0.851). The results obtained in the study help not only to clarify the effects of different ADH SNPs but to better understand how these polymorphisms modify each other's effects in the development of alcoholism and related diseases.

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“…An alternative explanation for the association between FLG mutations and alcohol sensitivity could be that FLG mutation carriers drink more alcohol to suppress itching in the skin. As expected for a Caucasian population,we have previously reported that the ALDH2 487lys variant known to be strongly related to alcohol sensitivity and drinking in Asians is extremely rare in our background population [43], and other less strong genetic variants may play a role in alcohol sensitivity.…”

Section: Discussionmentioning

confidence: 87%

Association between Loss-of-Function Mutations in the Filaggrin Gene and Self-Reported Food Allergy and Alcohol Sensitivity

Linneberg

Fenger

Husemoen

et al. 2013

Int Arch Allergy Immunol

Self Cite

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Background: Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy. Objective: We investigated the association of FLG mutations with self-reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol sensitivity. Methods: A total of 3,471 adults from the general population participated in a health examination. Information on food allergies, OAS and alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were defined as having at least one null mutation allele of R501X or 2282del4. Primary lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235 polymorphism. Results: FLG mutations were associated with a higher risk of self-reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI 1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI 1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum-specific IgE was measured in a subsample and confirmed the association between FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI was observed in relation to self-reported allergy to milk. Furthermore, FLG mutations were associated with a higher risk of alcohol sensitivity. Conclusions: We found that loss-of-function mutations in the FLG gene were significantly associated with self-reported food allergy and alcohol sensitivity, but not with OAS. These findings, if confirmed, support the idea that skin barrier functions may be involved in the pathogenesis of food allergy.

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The Association of ADH and ALDH Gene Variants With Alcohol Drinking Habits and Cardiovascular Disease Risk Factors

Cited by 54 publications

References 58 publications

Aldehyde Dehydrogenase 1B1: Molecular Cloning and Characterization of a Novel Mitochondrial Acetaldehyde-Metabolizing Enzyme

Aldehyde Dehydrogenase 1B1: Molecular Cloning and Characterization of a Novel Mitochondrial Acetaldehyde-Metabolizing Enzyme

Combined Effect of ADH1B RS1229984, RS2066702 and ADH1C RS1693482/ RS698 Alleles on Alcoholism and Chronic Liver Diseases

Association between Loss-of-Function Mutations in the Filaggrin Gene and Self-Reported Food Allergy and Alcohol Sensitivity

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