Tuesday, 27 March 2012

Predisposition for Alcoholism is Genetic



Callum Lister
42944074

Eye colour, height even heart disease are examples of genetic traits that are passed on from parent to offspring. Alcoholism has been long-debated, whether it is due to environmental influence or in-fact a genotype passed on from our parents.

Figure 1: Genetic factors increase risk
of alcoholism 
The genetic component for alcohol use disorder (AUD) has been supported by many studies. Genetic factors explain 40 to 60% of the variance that risk alcoholism[2]. Ramoz and colleagues[7] explain that alcoholism is a result of genetic, environmental (alcohol consumption), and social complexes influencing susceptible individuals. Multiple behavioural and physiological characteristics have been associated with alcohol dependence and manifest themselves in the form of anxiety, impulsivity, variations in the intensity of response to alcohol and alcohol-metabolizing patterns[8]. Genetic characteristics influence and contribute to the rate of development of alcohol dependence. This happens through pathways that determine the pathological effect on the brain, development of withdrawal symptoms and tolerance to intoxicating effects[5,3].


Figure 2: Chromosome 15 [6]   
Two strategies have been developed to identify which genes are related to alcoholism. The first is genome-wide analysis including whole genome linkage studies, which investigates the inheritance of loci (specific locations on a chromosome) within family lines[4,8]. The second strategy is candidate gene association studies, using case-control designs correlations are made between trait differences and genetic variants on a population. Using these strategies researchers have been able to identify susceptible regions on chromosome 1, 2, 4 and 7 with chromosome 2 also having protective and prone loci within the neurexin 1(NRXN1) gene[9]. Gamma-aminobutyric acid (GABA) receptor genes have also been associated with a region on chromosome 15. GABA is involved in the behavioural effects of alcohol including; anxiolysis, motor incoordination, ethanol preference and withdrawal signs[1].

Alcoholism is one of the most complex disorders, involving multiple genes and environmental and social influences that can differ from families and even individuals. Progress towards understanding the association between genetic vulnerability and alcoholism has been made. Studies have shown that there is more than one gene responsible for this disease. While a portion of finding between studies on genes and alcoholism have been inconsistent, the amount of studies done in the previous years has assisted in converging results on the same loci of particular chromosomes. Which supports the notion that genes in these areas are associated with alcoholism. The identiļ¬cation of these particular genes predisposing individuals to alcoholism could be used to recognise potential alcoholism in individuals and enhance prevention measures at an early stage.

References

[1] Buck, K (1996), Molecular genetic analysis of the role of GABAergic systems in the behavioral and cellular actions of alcohol, Behav Genet 26:313–323.

[2] Buscemi, L.,  Turchi, C (2011), An Overview of the Genetic Susceptibility to Alcoholism, Med Sci Law 51:2–6. (http://msl.rsmjournals.com.ezproxy.library.uq.edu.au/content/51/suppl_1/S2.full.pdf)

[3] Crabbe, J (2001), Use of Genetic Analyses to Refine Phenotypes Related to Alcohol Tolerance and Dependence, Alcoholism: Clinical and Experimental Research 25:288–292.

[4] Kimura, M,. Higuchi, S (2011) Genetics of Alcohol Dependence, Psychiatry and Clinical Neurosciences 65:213-225. (http://onlinelibrary.wiley.com.ezproxy.library.uq.edu.au/doi/10.1111/j.1440-1819.2011.02190.x/full)

[5] Koob, G., Le Moal, M (1997), Drug abuse: Hedonic homeostatic Dysregulation, Pub Med 278:52–58.

[6] Peele, S (2000), Limitations of Genetic Alcoholism and other Addictions, (http://www.bestdrugrehabclinic.com/2009/07/28/limitations-of-genetic-alcoholism-and-other-addictions/).

[7] Ramoz, N., Schumann, G., Gorwood, P (2006), Genetic and Pharmacogenetic Aspects of Alcohol-Dependence, Current Pharmacogenomics 4:19–32.

[8] Sloan, C., Sayarath, V., Moore, J (2006), Systems Genetics of Alcoholism, Retrieved on the 16/03/2012. http://pubs.niaaa.nih.gov/publications/arh311/14-25.htm.

[9] Yang, H., Chang, C., Lin, C., Chen, C., Fann, C (2005), A genome-wide scanning and fine mapping study of COGA data, BMC Genetics 6:S30.




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