Work in human has implicated a variant of the gene SLC39A8 (also known as ZIP8) in patterns of excessive alcohol consumption. SLC39A8 encodes a transmembrane solute carrier. There are multiple related genes in both human and fly; the most closely related gene in Drosophila is Zip71B. Genetic reagents generated for Zip71B include RNAi targeting constructs, overexpression constructs, and alleles caused by insertional mutagenesis.
Several UAS constructs of wild-type Hsap\SLC39A8 have been introduced into flies. Using an ics GAL4 driver, expression of the human gene resulted in a slight, but significant, resistance to ethanol-induced sedation.
Using again the ics GAL4 driver, reduced levels of Dmel\Zip71B effected by RNAi resulted in a reduction in initial resistance to ethanol-induced sedation (increased sensitivity); upon repeat exposure normal increased tolerance was observed. Similar results were obtained using transposon-insertion mutations of Dmel\Zip71B.
[updated Sep. 2023 by FlyBase; FBrf0222196]
Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).
The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)
Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).
Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]
SLC39A8 encodes a member of the SLC39 family of solute-carrier genes, which show structural characteristics of zinc transporters. The encoded protein is glycosylated and found in the plasma membrane and mitochondria. [Gene Cards, SLC39A8; 2023.09.06]
Multiple related genes in both species; most closely related to Dmel\Zip71B.
Multiple related genes in both species; moderate-scoring best-hit ortholog of SLC39A5, SLC39A14, SLC39A8, and SLC39A12.
