Aims: Alcoholism is a multifactorial, genetically influenced disorder. It is a major health and social issue, a highly frequent disease and a cause of premature death. It is also the most expensive addictive disorder due to morbidity, mortality, societal and legal problems. Besides their involvement in alcohol-related fatalities, forensic scientists are also required to assess driving and working ability as well as permanent invalidity due to alcohol-related conditions. Greater knowledge of the genetic basis of alcoholism could improve prevention by identifying specific risk factors and mechanisms, leading to effective therapeutic strategies and eventually to personalized treatments.
Methods: This overview of the recent scientific literature on the genetic basis of alcoholism summarizes the analytical strategies currently applied to the identification of candidate genes involved in alcohol-use disorders (AUDs) and discusses some genes and related phenotypes that have been shown to influence the risk of alcoholism.
Results: Alcoholism is a complex heterogeneous genetic disease. It is a quantitative disorder, in which the combined incidence of multiple genetic factors and environmental factors varies from one subject to another. Family, twin and adoption studies indicate that 50-60% of the risk of alcoholism is due to genetic factors. Risk loci for AUDs include both genes involved in alcohol pharmacokinetics and pharmacodynamics as well as genes moderating neurophysiological responses such as impulsivity, disinhibition, sensation-seeking and externalizing behaviours. Alcoholism also co-exists with other addictions and psychiatric disorders. Such co-morbidity suggests the existence of shared aetiological factors.
Conclusions: Despite several genes that influence the risk for AUDs having been identified, the genetic bases of alcoholism remain largely unknown. Particularly the mechanism of action or the understanding of the physiology of some genes, as well as the gene-environment interactions, is still unknown. Technological progress and advances in transcriptomics, epigenomics and proteomics are expected to enhance our knowledge of the genetic susceptibility to alcoholism.
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http://dx.doi.org/10.1258/msl.2010.010054 | DOI Listing |
Comb Chem High Throughput Screen
January 2025
Department of Endocrinology and Metabolism, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, China.
Aims And Objectives: This study aimed to explore the relationship between HERC6- associated immune response and Non-Alcoholic Fatty Liver Disease (NAFLD) and to screen drug candidates for novel treatments.
Materials And Methods: Mendelian Randomization (MR) was performed to test the relationship between a genetically predicted increase in HERC6 expression and the development of NAFLD. A single-cell RNA-seq profile of liver tissue with histological characteristics (GSE168933) was obtained.
Curr Med Chem
January 2025
Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disorders following liver transplantation. The prorenin receptor (PRR) plays a role in glucose and lipid metabolism, and the hepatic dysregulation of PRR is associated with the upregulation of several molecular pathways, such as the mammalian target of rapamycin (mTOR) and Peroxisome proliferator-activated receptor (PPAR) that promotes hepatic lipogenesis and leads to lipid accumulation in hepatocytes by upregulation of lipogenic genes. PRR inhibition leads to a reduction in the hepatic expression of sortilin-1 and low-density lipoprotein receptor (LDLR) levels and down-regulation of pyruvate dehydrogenase (PDH) and acetyl-CoA carboxylase (ACC) and reduces fatty acids synthesis in hepatocytes.
View Article and Find Full Text PDFCell Rep Med
December 2024
Capital Institute of Pediatrics, Beijing 100020, China. Electronic address:
We have previously reported that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the gut can cause endo-alcoholic fatty liver disease. Here, we discover that 91.2% of Kpn isolates from pulmonary disease samples also produce excess ethanol, which may be associated with respiratory disease severity.
View Article and Find Full Text PDFJAMA Health Forum
January 2025
Department of Health Policy and Management, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania.
Importance: 2021 Advance child tax credit (ACTC) monthly payments were associated with reduced US child poverty rates; however, policymakers have expressed concerns that permanent adoption would increase parental substance use.
Objective: To assess whether 2021 ACTC monthly payments were temporally associated with changes in substance use among parents compared with adults without children.
Design, Setting, And Participants: The primary sample included adults aged 18 to 64 years who responded to the National Survey on Drug Use and Health in 2021.
Hepatol Int
January 2025
Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
Background And Aims: Although beneficial in reducing the risk of bacterial infections in patients with advanced decompensated cirrhosis after upper gastrointestinal (GI) bleed, the utility of prophylactic antibiotics in those with Child-Pugh A cirrhosis is not known. We studied if prophylactic antibiotics can be withheld in this cohort.
Methods: This was a single-centre, open-label randomised-controlled-trial with non-inferiority design.
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