ADH1B*1, ADH1C*2, DRD2 (−141C Ins), and 5‐HTTLPR Are Associated With Alcoholism in Mexican American Men Living in Los Angeles

Konishi, Tamiko; Luo, Huai Rong; Calvillo, Maria; Mayo, Matthew S.; Lin, Keh Ming; Wan, Yu‐Jui Yvonne

doi:10.1097/01.alc.0000134231.48395.42

Cited by 69 publications

(68 citation statements)

References 59 publications

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“…There was, however, a substantial difference between East Asians and Caucasians, because a significant association between allele *2 and the risk of alcoholism was detected for the former (RE OR ϭ 1.91 [95% CI 1.45, 2.53]) but not the latter. In sensitivity analysis, 5,26,29,31,45 the pattern of results was also similar. In a subgroup analysis for the men 6,32,39 (no study provided data for women), there was no association.…”

Section: Adh2mentioning

confidence: 62%

“…Data from 50 studies that investigated the association between any of the ADH2, ADH3, CYP2E1, and ALDH2 polymorphisms and alcoholism, and alcohol-induced liver disease, met the inclusion criteria and were included in the meta-analysis. Thirty-three studies dealt with ADH2, 2 [2][3]6,8,11,[26][27][29][30][31][32]37,[39][40][41][42][43][44]46,47,51 and 20 studies in CYP2E1. 6,11,26,31,32,35,[41][42][43]54,[57][58][59][60][61][62][63][64][65]67 To investigate the association between any of the four loci considered and alcohol-induced liver disease, ten studies dealt with ADH2, 5,6,[31][32][33]35,…”

Section: Eligible Studiesmentioning

confidence: 99%

“…In studies of alcoholism, the distribution of genotypes in the control group departured from HWE in two studies for ADH2, 41,48 in five studies for ADH3, 5,26,29,31,45 in nine studies for ALDH2, 6,8,26,[29][30][31]47,51,56 and in two studies for CYP2E1. 11,60 Because a lack of HWE indicates possible genotyping errors and/or population stratification, a sensitivity analysis was performed excluding studies not in HWE.…”

Section: Summary Statisticsmentioning

confidence: 99%

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Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

et al. 2006

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Case-control studies that have investigated the association between alcoholism and alcoholinduced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2 polymorphisms have reported controversial or inconclusive results. Thus, we conducted a meta-analysis of 50 association studies of the above polymorphisms. We explored potential sources of heterogeneity and bias, performed subgroup analyses by racial background and sex, performed sensitivity analyses for studies not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases that met strict criteria for alcoholism. The present meta-analysis underscores significant associations of ADH2*1, ADH3*2, and ALDH2* . When strict criteria were imposed, the pattern of results remained unaltered. For liver disease, there were no significant associations for ADH2*1, ADH3*2, or ALDH2*1 in all subpopulations. The CYP2E1 polymorphism showed no association whatsoever. There is evidence that alleles are mainly dominant. In conclusion, there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2, and lack of bias in all polymorphisms. The above findings reinforce the need for more rigorous studies, and for regular synthesis of studies' results. O ver the last few years, an increasing number of studies have provided compelling evidence for the involvement of genetically defined predisposing factors in alcoholism and alcohol-induced cirrhosis. The strongest support comes from the fact that not all subjects with a high daily intake of alcohol develop alcohol-induced liver disease. Mostly metabolized in the liver by the successive action of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the rate of conversion of ingested ethanol to acetaldehyde, and of acetaldehyde to acetate, is influenced by genetic polymorphisms at both loci. ALDH2 is the most important gene that affects predisposition to alcoholism in Asian populations. Thus, the prevalence in these populations of the inactive ALDH enzymatic form encoded by the ALDH2*2 allele appears to protect against alcoholism. 1 Furthermore, alcoholics with this inactive allele may be at great risk for advanced alcoholic liver disease. [2][3][4] Regarding the ADH gene cluster, polymorphisms are also detected at the ADH2 and ADH3 loci with two alleles (referred to as *1 and *2) each. Alleles ADH2*2 and ADH3*1 encode, respectively, for the highly active ␤ 2 and ␥ 1 allozymes, 5 and a low prevalence of both alleles has been reported in alcoholic Asians-although some studies did not detect associations between ADH3 polymor-

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Section: Adh2mentioning

confidence: 62%

Section: Eligible Studiesmentioning

confidence: 99%

Section: Summary Statisticsmentioning

confidence: 99%

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Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

et al. 2006

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“…The hazard ratio of hospitalization for alcoholism in men and women with the slow alcohol degradation ADH1B Á 1/1 genotype was 3.9 (95% CI: 1.0-16) and 2.7 (95% CI: 0. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

Section: Resultsmentioning

confidence: 99%

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

et al. 2007

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Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B Á 1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B Á 1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B Á 1/1 genotype compared to men with the ADH1B Á 1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C Á 1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B Á 2/2 genotype, compared with men with the ADH1C Á 1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B Á 1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

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“…There is strong evidence for a negative association between the ADH1B*2 allele (i.e., A allele at rs1229984) and alcohol dependence and alcohol consumption (Ehlers et al, 2012;Konishi et al, 2004;Li et al, 2011;Macgregor et al, 2009), as well as evidence for the ADH1B*3 allele (i.e., T allele at rs2066702) (Edenberg et al, 2006;Ehlers et al, 2007). Bierut et al (2012) reported reduced risk for alcohol dependence for the A allele at rs1229984 versus the G/G genotype in a combined sample of European Americans and African Americans.…”

mentioning

confidence: 99%

Interactions Between Alcohol Metabolism Genes and Religious Involvement in Association With Maximum Drinks and Alcohol Dependence Symptoms

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Dick

Almasy

et al. 2016

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Variations in the genes encoding alcohol dehydrogenase (ADH) enzymes are associated with both alcohol consumption and dependence in multiple populations. Additionally, some environmental factors have been recognized as modifiers of these relationships. This study examined the modifying effect of religious involvement on relationships between ADH gene variants and alcohol consumption-related phenotypes. Method: Subjects were African American, European American, and Hispanic American adults with lifetime exposure to alcohol (N = 7,716; 53% female) from the Collaborative Study on the Genetics of Alcoholism. Genetic markers included ADH1B-rs1229984, ADH1B-rs2066702, ADH1C-rs698, ADH4-rs1042364, and ADH4-rs1800759. Phenotypes were maximum drinks consumed in a 24-hour period and total number of alcohol dependence symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Religious involvement was defined by self-reported religious services attendance. Results: Both religious involvement and ADH1B-rs1229984 were negatively associated with the number of maximum drinks consumed and the number of lifetime alcohol dependence symptoms endorsed. The interactions of religious involvement with ADH1B-rs2066702, ADH1C-rs698, and ADH4-rs1042364 were significantly associated with maximum drinks and alcohol dependence symptoms. Risk variants had weaker associations with maximum drinks and alcohol dependence symptoms as a function of increasing religious involvement. Conclusions: This study provided initial evidence of a modifying effect for religious involvement on relationships between ADH variants and maximum drinks and alcohol dependence symptoms. (J. Stud. Alcohol Drugs, 77, 393-404, 2016)

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ADH1B1, ADH1C2, DRD2 (−141C Ins), and 5‐HTTLPR Are Associated With Alcoholism in Mexican American Men Living in Los Angeles

Abstract: Together, the data reveal unique genetic patterns in Mexican Americans that may be in part responsible for the heightened risk for alcoholism and alcohol-associated health problems in this population.

Cited by 69 publications

References 59 publications

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

Interactions Between Alcohol Metabolism Genes and Religious Involvement in Association With Maximum Drinks and Alcohol Dependence Symptoms

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