CYP2E1*1D regulatory polymorphism: association with alcohol and nicotine dependence

OBJECTIVE: CYP2E1 bioactivates environmental protoxins and metabolizes alcohol. CYP2E1 is induced by alcohol and cigarette smoking and may contribute to metabolic tolerance in alcoholics. The CYP2E1*1D polymorphism has been associated with greater CYP2E1 inducibility. One objective was to determine the frequency of the variant allele in eight ethnic groups. Further, the Canadian Native Indian, South-east Asian Canadian and Caucasian Canadian groups were stratified by alcohol and nicotine dependence (as measured by DSM-IV criteria) to examine the potential association of CYP2E1*1D with drug dependence. RESULTS AND CONCLUSIONS: We found a significantly greater frequency of the CYP2E1*1D allele among Indo-Asian Canadians (0.31), Chinese Canadians (0.19), Taiwanese (0.20), Japanese Canadians (0.18), African Americans (0.13), African Canadians (0.10) and Canadian Native Indians (0.09) compared to Caucasian Canadians (0.02). Although the power of the association study was low among some subgroups, the CYP2E1*1D genotype (subjects with at least one variant allele) was associated with alcohol as well as nicotine dependence. Specifically, Canadian Native Indians dependent on nicotine alone or alcohol alone exhibited significantly greater CYP2E1*1D frequencies compared to non-drug dependent controls, while the variant frequency among Southeast Asians dependent on nicotine was greater than their non-drug dependent counterparts. We also found that CYP2E1*1D genotype was associated with significantly greater 3-hydroxycotinine per cigarette in African Americans. The variable frequency of CYP2E1*1D among ethnic groups suggests a greater risk for diseases putatively related to CYP2E1 in some non-Caucasian ethnic groups. The association of CYP2E1*1D with alcohol and nicotine dependence suggests that CYP2E1 may contribute to the development of these dependencies.     

Involvement of the mu-opioid receptor gene polymorphism A118G in the efficacy of detoxification of alcohol dependent patients

Introduction

The A118G (rs 1799971) polymorphism in the mu-opioid receptor gene (OPRM1) has been reported to be associated with alcohol addiction.

Methods

In this study 109 patients diagnosed with alcohol dependence in accordance with DMS-IV criteria and 95 healthy subjects were enrolled and everyone has been genotyped.

Results

The percentage of alcoholic patients with higher than normal gamma-glutamyl transferase (GGT) levels significantly decreased after six months of standard detoxification treatment, both in patients with A/A genotype and in the other ones with A/G genotype. However, the percentage of alcohol dependent patients with the A/A genotype recorded a slight decrease of the GGT and the mean corpuscolar volume of erythrocytes (MCV) combination marker after six months of therapy (30% vs 12%), while subjects with the A/G genotype showed no variation.

Conclusion

This finding suggests that alcohol dependent patients with the A/A genotype could have a faster restoration of their liver function than those ones with the A/G genotype: it might be possible that the presence of G allele confers on these patients a reduced ability in abstaining from drinking alcohol.     

Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians

Genetically variable CYP2A6 is the primary enzyme that inactivates nicotine to cotinine. Our objective was to investigate allele frequencies among five ethnic groups and to investigate the relationship between genetically slow nicotine metabolic inactivation and smoking status, cigarette consumption, age of first smoking and duration of smoking. Chinese, Japanese, Canadian Native Indian, African-North American and Caucasian DNA samples were assessed for CYP2A6 allelic frequencies (CYP2A6*1B-*12,*1x2). Adult Caucasian non-smokers (n = 224) (1-99 cigarettes/lifetime) and smokers (n = 375) (> or = 100 cigarettes/lifetime) were assessed for demographics, tobacco/drug use history and DSM-IV dependence and genotyped for CYP2A6 alleles associated with decreased nicotine metabolism (CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*12). CYP2A6 allele frequencies varied substantially among the ethnic groups. The proportion of Caucasian slow nicotine inactivators was significantly lower in current, DSM-IV dependent smokers compared to non-smokers [7.0% and 12.5%, respectively, P = 0.03, odds ratio (OR) = 0.52; 95% confidence interval (CI) 0.29-0.95]; non-dependent smokers showed similar results. Daily cigarette consumption (cigarettes/day) was significantly (P = 0.003) lower for slow (21.3; 95% CI 17.4-25.2) compared to normal inactivators (28.2; 95% CI 26.4-29.9); this was observed only in DSM-IV dependent smokers. Slow inactivators had a significantly (P = 0.03) lower age of first smoking compared to normal inactivators (13.0 years of age; 95% CI 12.1-14.0 versus 14.2; 95% CI 13.8-14.6), and a trend towards smoking for a shorter duration. This study demonstrates that slow nicotine inactivators are less likely to be adult smokers (dependent or non-dependent). Slow inactivators also smoked fewer cigarettes per day and had an earlier age of first smoking (only dependent smokers).     

D2 dopamine receptor gene polymorphism: paroxetine and social functioning in posttraumatic stress disorder.

This study examined whether allelic status of the D2 dopamine receptor (DRD2) gene was associated with response to a selective serotonin reuptake inhibitor, paroxetine, in the treatment of posttraumatic stress disorder (PTSD). Sixty-three Caucasian war veterans with combat-related PTSD were treated with paroxetine for 8 weeks. Patients were assessed at baseline and at follow-up using the General Health Questionnaire-28 (GHQ). TaqI A DRD2 alleles were determined by PCR. Before paroxetine treatment, patients with the DRD2 A1+ allele (A1A2 genotype) compared to those with the A1- allele (A2A2 genotype) had higher total GHQ psychopathological scores (P=0.040) and higher GHQ subscale scores for anxiety/insomnia (0.046), social dysfunction (P=0.033) and depression (P=0.011). In an intention-to-treat analysis, paroxetine was associated with significant improvement in total GHQ scores (P=0.014) and in the factor scores of social dysfunction (P=0.033), anxiety (P=0.009) and depression (P=0.026). Furthermore, there was a significant allele by time interaction on the social dysfunction scale, with A1+ allelic patients showing significant improvement in social functioning compared to A1- allelic patients (P=0.031), an effect independent of changes in depression or anxiety. This suggests changes in social functioning induced by paroxetine may be, in part, mediated via D2 dopamine receptors. The DRD2 A1 allele may prove to be a useful marker to assist clinicians in predicting which patients with PTSD are likely to obtain improvements in social functioning with paroxetine treatment.     

Difference between alcohol dependence and nicotine dependence in cognitive dysfunction]

The extent of cognitive dysfunction in the nicotine and/or alcohol dependent subjects has been evaluated with Digit Span, Number Connection Test and Wisconsin Card-Sorting Test. Samples were divided into 4 groups, 8 subjects with alcohol and nicotine dependence, 9 subjects with alcohol dependence, 10 subjects with nicotine dependence and 31 subjects without the dependences who met ICD-10 criteria for dependence syndrome. The performance times of Number Connection Test were prolonged in the alcohol dependence and the presence of the nicotine dependence did not influence the performance times of Number Connection Test. The performances on the Wisconsin Card-Sorting Test were impaired by the alcohol dependence and the presence of the nicotine dependence did not influence the performances on the Wisconsin Card-Sorting Test.     

Smoking cessation and alcohol consumption in individuals in treatment for alcohol use disorders

Most individuals with alcohol use disorders are dependent on both alcohol and nicotine, and combined use of both substances is more damaging to health than use of either alone. Although research indicates that alcoholics can quit smoking, discrepant results have been reported regarding whether smoking cessation is associated with increased risk of alcohol relapse. The purpose of this paper was to examine the relationship between smoking cessation and alcohol consumption using data from Project MATCH. Of the 1,307 participants who smoked at any point during the study, 160 (12%) quit. Quitters consumed less alcohol than those who continued smoking. In addition, quitters demonstrated a significant reduction in alcohol consumption at the time of smoking cessation, which was sustained for six months post-cessation. These findings suggest that individuals in treatment for alcohol use disorders who are motivated to stop smoking can safely be encouraged to do so without jeopardizing their sobriety.     

Measures of Substance Consumption Among Substance Users, DSM-IV Abusers, and Those With DSM-IV Dependence Disorders in a Nationally Representative Sample

ABSTRACT. Objective: Neither the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R), nor the DSM-IV uses measures of substance consumption as part of the diagnostic criteria for substance use disorders. Therefore, this report examined the extent to which frequency and/or quantity of consumption across a broad spectrum of substances are associated with DSM-IV diagnoses of specific substance use disorders and whether there are informative hierarchical levels of consumption among users, abusers, and those who are substance dependent in the U.S. general population. Method: The analyses focused on consumption data from respondents of the 2001-2002 National Epidemiologic Survey of Alcohol and Related Disorders. Multinomial logistic regression was used to predict DSM-IV diagnoses of dependence or abuse based on the continuous consumption measures. Results: Among individuals who used substances, the substances with the greatest liability for dependence were nicotine first and cocaine second. For nearly all substances investigated, users without specific substance use disorders demonstrated lower levels of quantity and frequency of consumption relative to those with DSM-IV abuse and dependence disorders. Dose-response curves for the log odds of abuse and dependence suggested unidimensionality of abuse and dependence for frequency of alcohol drinking; frequency of cannabis use; frequency of opioid use; frequency of hallucinogen use; and, to a lesser extent, frequency of amphetamine use. However, the dose-response curves for the quantity of alcohol consumed demonstrated differential patterns for abuse and dependence such that alcohol dependence has a distinctly greater "quantity of use" relationship than that found among alcohol-abusing individuals. Conclusions: These results confirm the findings of others concerning the unidimensionality of abuse and dependence diagnoses when consumption variables alone are examined and suggest that consumption measures may be useful metrics gauging severity. (J. Stud. Alcohol Drugs, 73, 820-828, 2012).     

Associations of ALDH2 and ADH1B genotypes with response to alcohol in Asian Americans

OBJECTIVE: Individuals with alcohol dependence are less likely to possess variant alleles of the alcohol-metabolizing genes, aldehyde dehydrogenase (ALDH2*2) and alcohol dehydrogenase (ADH1B*2), than non-alcohol-dependent controls. It is hypothesized that the mechanism through which these alleles protect against alcohol dependence is by causing elevations in acetaldehyde, which in turn cause an increased response to alcohol. Previous research has shown that individuals with ALDH2*2 demonstrate enhanced reactions to alcohol compared with those without this genetic variant, but evidence that ADH1B*2 is associated with a greater alcohol response is mixed. This study was designed to determine whether the ADH1B genotype is associated with more intense reactions to alcohol after controlling for the ALDH2 genotype. METHOD: Participants (N = 101) were Asian American college students. Each was evaluated using objective and subjective measures before and after ingestion of alcohol and placebo beverages. RESULTS: Participants with the ALDH2*1/*2 and ALDH2*2/*2 genotypes were more likely to experience vomiting following ingestion of the alcohol beverage than those with the ALDH2*1/*1 genotype. Participants with the ALDH2*1/*2 genotype also had greater pulse-rate increases, observed flushing ratings, and subjective feelings of intoxication 30 minutes after ingestion of alcohol than participants with the ALDH2*1/*1 genotype, despite equivalent blood alcohol concentration (BAC) measurements. Among participants with the ALDH2*1/*1 genotype, there were no additional effects of the ADH1B genotype on any measures of response to alcohol. Among participants with the ALDH2*1/*2 genotype, those with the ADH1B*2/*2 genotype were more likely to experience alcohol-induced vomiting and to report feeling less "great overall" 30 minutes after ingestion of alcohol than those with the ADH1B*1/*2 genotype. CONCLUSIONS: These findings are consistent with the hypothesis that there is an additional effect of ADH1B*2 on level of response to alcohol, but only among individuals with the ALDH2*1/*2 genotype.     

The impact of past alcohol use on treatment response rates in patients with chronic hepatitis C

BACKGROUND: Studies have shown that past alcohol consumption reduces response rates in patients with chronic hepatitis C treated with interferon monotherapy. AIM: To clarify the importance of alcohol consumption on response rates in patients undergoing treatment with pegylated interferon and ribavirin. METHODS: In a single centre, prospective study, median daily alcohol consumption (determined by previously validated method) and quartiles of alcohol consumption were calculated. Univariate and binary logistic regression analyses were performed using treatment response status as the dependent variable. RESULTS: Overall, in an intention-to-treat analysis, 34 of 115 patients (30%) responded to treatment. In univariate analysis, black patients, especially those with hepatitis C virus genotype 1, high viral load and low alanine aminotransferase were significantly less likely to respond. Predictors of response by regression analysis included alcohol <30 g/day (OR=3.02, 95% CI: 1.02-8.93; P=0.04), non-genotype 1 status (OR=1.98, 95% CI: 1.03-3.80; P=0.04) and non-black race (OR=2.79, 95% CI: 1.33-5.85; P=0.006). CONCLUSIONS: Median daily alcohol use >30 g/day is associated with failure to respond to pegylated interferon and ribavirin for treatment of hepatitis C. Past alcohol use should be evaluated when considering treatment for hepatitis C.     

Influence of the dopamine D2 receptor (DRD2) exon 8 genotype on efficacy of tiapride and clinical outcome of alcohol withdrawal.

We tested the hypothesis that allelic variants of the human dopamine D2 receptor E8 genotype are associated with (i) dopamine D2 antagonist tiapride dose in treatment of alcohol withdrawal (n = 50) and (ii) with anxiety and depression in patients during alcoholism detoxification therapy (admission n = 87; discharge n = 50). DRD2 E8 A/A genotype was associated with increased dose of tiapride during a 9-day detoxification therapy and with increased anxiety and depression scores on admission and 2 weeks later. The findings suggest a pharmacogenetic influence of DRD2 E8 genotype on tiapride efficacy in alcohol withdrawal. In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the dopamine D2 agonist apomorphine; however, it is not clear whether both findings share the same biological basis. Earlier findings concerning association of DRD2 E8 A/A with increased anxiety and depression are replicated for the first time.     

Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice

Recent advances in the understanding of the neurobiological basis of alcohol dependence suggest that the endocannabinoid system may play a key role in the reinforcing effects of ethanol. In the present study, disruption of CB1 receptors in mice generated on a CD1 background decreased both ethanol consumption and preference. This decreased ethanol self-administration was associated with increased sensitivity to the acute intoxicating effects of ethanol. Mutant mice were more sensitive to the hypothermic and sedative/hypnotic effects of acute ethanol administration (1.5-4.0 g/kg), although plasma ethanol concentrations did not differ from those of controls. Moreover, wild-type mice exhibited normal locomotor activation caused by 1.0-2.5 g/kg injection of ethanol, whereas mutant mice displayed sedation in response to the injection of the same ethanol doses. The severity of alcohol withdrawal-induced convulsions was also increased in CB1(-/-) mice. Our results suggest that CB1 receptors participate in the regulation of ethanol drinking and demonstrate that their disruption lead to increased ethanol sensitivity and withdrawal severity.     

Symptoms of alcohol dependence and smoking initiation and persistence: A longitudinal study among US adults

Background

A large number of adults report symptoms of, but do not meet diagnostic criteria for, an alcohol use disorder. Yet, little is known about the relationship between symptoms of alcohol use disorders and the initiation and persistence of smoking. This study prospectively examines the relationship between having 1–2 symptoms of alcohol dependence (without abuse) and smoking initiation and persistence as well as nicotine dependence over a 3-year period among adults in the United States.

Methods

Data were drawn from Wave 1 (2001–2002) and Wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Relationships between Wave 1 symptoms of alcohol dependence, alcohol abuse, and alcohol dependence and initiation and persistence of cigarette smoking and nicotine dependence at Wave 2 were examined using logistic regression analyses. Analyses were adjusted for demographics, mood and anxiety disorders.

Results

Symptoms of alcohol dependence were associated with smoking initiation at Wave 2. There was no association between symptoms of alcohol dependence and smoking persistence. Symptoms of alcohol dependence predicted incident and persistent nicotine dependence. Findings persisted after adjusting for demographic characteristics and mood/anxiety disorders.

Conclusions

Even 1–2 symptoms of alcohol dependence are associated with increased vulnerability to smoking initiation and onset and persistence of nicotine dependence at a similar strength as alcohol use disorders. Efforts at smoking cessation must address problematic alcohol use, even at the subclinical level, in order to improve efficacy.     

Diagnosing alcohol abuse in alcohol dependent individuals: Diagnostic and clinical implications

In DMS-IV, the diagnosis of alcohol abuse is precluded by the diagnosis of alcohol dependence. The goal of this study was to examine the diagnostic and clinical implications of diagnosing alcohol abuse among alcohol dependent individuals. Treatment-seeking psychiatric outpatients with a lifetime history of alcohol dependence (n = 544), some of whom (n = 45) did not meet lifetime criteria for alcohol abuse completed in-depth, face-to-face, semi-structured clinical assessments of DSM-IV axis I and axis II psychopathology. Alcohol dependent patients who did not meet criteria for alcohol abuse were significantly more likely to be female, have a later age of onset for alcohol dependence, have fewer dependence symptoms, and have a lower rate of positive family history for alcoholism, and were less likely to report a lifetime history of DSM-IV drug use disorders and PTSD. These findings suggest that diagnosing alcohol abuse among alcohol dependent patients may be clinically useful as an index of severity and higher likelihood of comorbid drug abuse and dependence. Future studies are needed to establish whether these differences are clinically significant in terms of the course of the disorder and response to treatment.     

Unaided smoking cessation among smokers in treatment for alcohol dependence

To investigate the possible impact of treatment of alcohol dependence on smoking, we studied 144 smokers in an alcohol treatment center for whom 6-month data were available. Of those, 18 reported not smoking at 6 months. No significant differences in age, gender, or race were observed between quitters and continuing smokers. Quitters at 6 months were significantly more likely to be low dependent smokers than were continuing smokers and were significantly more likely to report no drinking during the past 28 days at the end of 1 month's treatment (93%) than continuing smokers (62%). These findings suggest that quitting smoking may be associated with low levels of nicotine dependence and favorable alcohol treatment response in alcoholic smokers.     

Marital status, alcohol dependence, and GABRA2: evidence for gene-environment correlation and interaction

OBJECTIVE: The gene GABRA2 has been associated with the risk for alcohol dependence in independent samples. This article explores how this genetic risk factor interacts with marital status, another factor previously shown to be associated with the risk for alcohol dependence. METHOD: Data from more than 1,900 male and female subjects from the Collaborative Study of the Genetics of Alcoholism (COGA) sample were analyzed. Subjects were recruited based on membership in a family with multiple individuals with alcoholism. A series of analyses was performed to evaluate the relationship between the following: (1) GABRA2 and alcohol dependence, (2) marital status and alcohol dependence, (3) GABRA2 and marital status, and (4) interactions between GABRA2 and marital status on the development of alcohol dependence in the high-risk COGA sample. Additional analyses were carried out in a sample of approximately 900 individuals from control families to test the generalizability of results. RESULTS: Both GABRA2 and marital status contributed independently to the development of alcohol dependence in the COGA sample. The high-risk genotype at GABRA2 was also related to a decreased likelihood of marrying and an increased likelihood of divorce, which appeared to be mediated in part by personality characteristics. There was also differential risk associated with the GABRA2 genotype according to marital status. CONCLUSIONS: These analyses provide evidence of both gene-environment correlation and gene-environment interaction associated with GABRA2, marital status, and alcohol dependence. They illustrate the complex pathways by which genotype and environmental risk factors act and interact to influence alcohol dependence and challenge traditional conceptualizations of "environmental" risk factors.     

Genetic influences on craving for alcohol

Introduction

Craving is being considered for inclusion in the Diagnostic and Statistical Manual (DSM) DSM-5. However, little is known of its genetic underpinnings — specifically, whether genetic influences on craving are distinct from those influencing DSM-IV alcohol dependence.

Method

Analyses were conducted in a sample of unrelated adults ascertained for alcohol dependence (N = 3976). Factor analysis was performed to examine how alcohol craving loaded with the existing DSM-IV alcohol dependence criteria. For genetic analyses, we first examined whether genes in the dopamine pathway, including dopamine receptor genes (DRD1, DRD2, DRD3, DRD4) and the dopamine transporter gene (SLC6A3), which have been implicated in neurobiological studies of craving, as well as alpha-synuclein (SNCA), which has been previously found to be associated with craving, were associated with alcohol craving in this sample. Second, in an effort to identify novel genetic variants associated with craving, we conducted a genomewide association study (GWAS). For variants that were implicated in the primary analysis of craving, we conducted additional comparisons — to determine if these variants were uniquely associated with alcohol craving as compared with alcohol dependence. We contrasted our results to those obtained for DSM-IV alcohol dependence, and also compared alcohol dependent individuals without craving to non-dependent individuals who also did not crave alcohol.

Results

Twenty-one percent of the full sample reported craving alcohol. Of those reporting craving, 97.3% met criteria for DSM-IV alcohol dependence with 48% endorsing all 7 dependence criteria. Factor analysis found a high factor loading (0.89) for alcohol craving. When examining genes in the dopamine pathway, single nucleotide polymorphisms (SNPs) in DRD3 and SNCA were associated with craving (p < 0.05). There was evidence for association of these SNPs with DSM-IV alcohol dependence (p < 0.05) but less evidence for dependence without craving (p > 0.05), suggesting that the association was due in part to craving. In the GWAS, the greatest evidence of association with craving was for a SNP in the integrin alpha D (ITGAD) gene on chromosome 7 (rs2454908; p = 1.8 × 10^− 6). The corresponding p-value for this SNP with DSM-IV alcohol dependence was similar (p = 4.0 × 10^− 5) but was far less with dependence without craving (p = 0.02), again suggesting the association was due to alcohol craving. Adjusting for dependence severity (number of endorsed criteria) attenuated p-values but did not eliminate association.

Conclusions

Craving is frequently reported by those who report multiple other alcohol dependence symptoms. We found that genes providing evidence of association with craving were also associated with alcohol dependence; however, these same SNPs were not associated with alcohol dependence in the absence of alcohol craving. These results suggest that there may be unique genetic factors affecting craving among those with alcohol dependence.     

Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction

BackgroundWeinvestigated the relationship between withdrawal syndrome symptoms and dopamine receptor 2 DRD2 gene polymorphisms -141 C I/D (rs1799732) exon 8 G/A (rs6276) and ANKK1 (Ankyrin Repeat and Kinase Domain Containing 1) gene polymorphism Taq 1 A (rs1800497).MaterialA total number of 213 patients who met the ICD 10 criteria for given phenotypes were enrolled in the study. Those phenotypes included: dissocial personality disorder, early onset, alcohol withdrawal syndrome with seizures, alcohol withdrawal syndrome with delirium tremens, and alcohol withdrawal syndrome with seizures and delirium tremens.ResultsOur results show statistically significant associations between SNP in exon 8 A/G in the DRD2 gene and alcohol withdrawal syndrome with seizures, and between SNP in promoter -141 C I/D in the DRD2 gene and early onset of alcohol dependence (AD). The A/A genotype in exon 8 A/G polymorphism seems to be a positive predictive factor for the presence or the lack of seizures in alcohol withdrawal syndrome. The A/G genotype is possibly a protective factor for this AD phenotype.ConclusionsThese results suggest that both investigated DRD2 polymorphisms have an impact onthe AD phenotype. The findings of the presented study reconfirm that dopamine receptor 2 gene polymorphisms are associated with alcohol addiction and alcohol withdrawal syndrome.     

Drinking patterns among individuals with and without DSM-IV alcohol use disorders

OBJECTIVE: The purpose of this study was to compare alcohol consumption patterns among individuals with and without alcohol use disorders, using a representative sample of the general population that would not exaggerate differences as a result of selection biases associated with treatment for alcohol problems. METHOD: Based on data from 18,352 past-year drinkers selected from a nationally representative sample of U.S. households, 11 measures of past-year alcohol consumption were compared for three diagnostic groups: (1) individuals who did not meet the criteria for either alcohol abuse or dependence, i.e., those without a DSM-IV alcohol use disorder (AUD); (2) those classified with abuse only; and (3) those classified with alcohol dependence, with or without abuse. RESULTS: For all measures reflecting frequency and quantity of drinking, frequency of heavy drinking and intoxication, and frequency of atypical temporal drinking patterns, the values for abusers lay midway between those for individuals without an AUD and those with dependence. Individuals with alcohol use disorders drank a greater proportion of their ethanol intake in the form of beer and a lower proportion in the form of wine than did those without an AUD. Of all the consumption measures considered, frequency of intoxication showed the strongest association with the probability of having an AUD, followed by frequency of drinking 5 + drinks, prevalence of morning drinking and total volume of intake. The ratios of consumption measures for individuals with disorders relative to those without an AUD showed relatively little significant variation across demographic subgroups of the population. CONCLUSIONS: The findings supported the distinction between the disorders of alcohol abuse and dependence, and implicated loss of control as an important element of this distinction. They also indicated that even among individuals with alcohol use disorders, demographic differentials reflecting cultural, physiological and normative forces were maintained and should be considered in approaches to treatment.     

Five exon 1 variants of mu opioid receptor and vulnerability to alcohol dependence

The human mu opioid receptor (hMOR) gene is a prime candidate gene responsible for addictive disorders. The present association study tested the hypothesis that hMOR exon 1 variants elicit susceptibility to alcohol dependence. We have analyzed five nucleotide changes in exon 1 of the hMOR gene. Three of them are in the 5'untranslated region of exon 1 at positions -172G/T,-111C/T and -3 8C/A, the remaining two variants cause amino acid substitutions: +17C/T (Ala6Val) and +118A/G (Asn40Asp). Our population-based association study included 327 German alcohol-dependent subjects and 340 ethnically matched controls. The lack of an allelic association suggests that the analyzed hMOR exon 1 variants do not contribute a common and substantial effect to the genetically determined vulnerability of alcohol dependence.