Abstract
Aims: Different vulnerability genes have been proposed in alcohol dependence, but replications are sparse, probably due to 1) phenotypical heterogeneity and 2) difficulties to rely on reliable definition of the correct phenotype. Indeed, specific subgroups of patients may be more directly concerned with some vulnerability genes, the actions of these genes being more directly related to their function. We postulated that three potential vulnerability genes, that were at least twice associated with alcohol dependence, influence the extreme of the severity of alcohol dependence, i.e. mortality, through traits with which they were previously associated, namely impulsivity and antisocial personality disorder and the 5-HT1B gene, suicide attempt and the short allele of 5-HTTLPR, and addictive disorder comorbidity and the DRD2 gene. Methods: We analysed the survival status of a male alcohol-dependent sample (n = 126) recruited 9 years before, and could compare 61 surviving patients to 41 patients who died during this period (representing 81.0% of the initial sample). Results: The main clinical characteristic that was associated with an increased mortality rate was a larger cumulative tobacco use (pack-years). We also found that the C allele of the 5-HT1b was the only one in excess in the non-surviving patients. Contrary to our hypothesis, impulsivity and antisocial personality disorder were not explaining the role of this gene. Conclusions: Even if there is a significant involvement of the 5- HT1B C allele, no intermediate phenotype was detected in our sample. The relatively short delay of 9 years and the somewhat old age at baseline of our patients could have limited the influence of psychiatric comorbidity or the specificities of alcohol dependence, explaining why the only detected co-factor was tobacco consumption. Tobacco dependence is therefore the main factor to explain mortality within the first decade, and the effect of this comorbid condition is not explained by three vulnerability genes previously associated to alcohol dependence.
Highlights
Alcohol dependence has a dramatic mortality rate [1]
We postulated that three potential vulnerability genes, that were at least twice associated with alcohol dependence, influence the extreme of the severity of alcohol dependence, i.e. mortality, through traits with which they were previously associated, namely impulsivity and antisocial personality disorder and the 5-HT1B gene, suicide attempt and the short allele of 5-HTTLPR, and addictive disorder co-morbidity and the DRD2 gene
Such co-morbidity could further deteriorate the survival prognosis, as in a study based on 500 outpatients, the presence of one of these psychiatric disorders increased by two the mortality rate at seven years, when compared with the general population [5]
Summary
Alcohol dependence is frequently associated with other psychiatric disorders, such as antisocial personality, attention deficit-hyperactivity, mood or schizophrenia disorders [3,4] Such co-morbidity could further deteriorate the survival prognosis, as in a study based on 500 outpatients, the presence of one of these psychiatric disorders increased by two the mortality rate at seven years, when compared with the general population [5]. Ninety percent of alcoholic patients are smokers [7], the prevalence of alcoholism reaching 10 times higher among smokers than nonsmokers [8] These risks factors have been shown to interact to modify the global prognosis, as for example tobacco smoking enhances ethanol induced pancreatic injury [9]
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