Journal of Alcoholism & Drug Dependence
Open Access

The Impact of Neurotransmitter System Genetic Variations in the Development and Treatment of Alcoholism

Andreana Sophi^{* *}Correspondence: Andreana Sophi, Department of Medicine, University of Auckland, Auckland, New Zealand, Email:

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Description

Alcohol dependence is a complex disorder influenced by genetic and environmental factors. Various studies have investigated the role of genetic polymorphisms in neurotransmitter systems in the development and progression of alcohol dependence. One such target of interest is the Norepinephrine Transporter (NET), a protein involved in the reuptake of norepinephrine from the synapse. Two common polymorphisms in the NET gene, T-182C and G1287A, have been suggested as potential contributors to alcohol dependence. However, recent research challenges the association between these polymorphisms and alcohol dependence, along with its clinical subgroups. This article aims to explore the current scientific evidence and shed light on the lack of association between T-182C and G1287A NET polymorphisms and alcohol dependence.

The role of norepinephrine transporter

The Nor-epinephrine Transporter (NET) plays a crucial role in regulating the reuptake of norepinephrine, a neurotransmitter involved in various physiological and psychological processes. Given the neurotransmitter's involvement in stress response, arousal, and reward pathways, it has been proposed that dysregulation of the norepinephrine system may contribute to alcohol dependence.

The T-182C polymorphism is located in the promoter region of the NET gene, while G1287A is a non-synonymous polymorphism that leads to an amino acid change in the protein structure. These polymorphisms have attracted attention due to their potential impact on the expression and function of the NET protein, thus potentially influencing the risk of alcohol dependence. Numerous studies have attempted to investigate the association between T-182C and G1287A polymorphisms and alcohol dependence, but the findings have been inconsistent. Several early studies reported positive associations, suggesting that individuals with specific variants of these polymorphisms may be more susceptible to alcohol dependence.

Lack of consistency: Numerous studies exploring the T-182C and G1287A polymorphisms have yielded inconsistent results. Some investigations have found weak associations, while others have found no significant link. The lack of consistent evidence raises doubts about the reliability of these genetic markers as predictors of alcohol dependence.

Sample size limitations: Many earlier studies had relatively small sample sizes, making it difficult to draw definitive conclusions. The statistical power of these studies may have been insufficient to detect subtle effects, leading to false positive or negative results.

Heterogeneity of alcohol dependence: Alcohol dependence is a complex disorder with multiple clinical subgroups. These subgroups may vary in terms of underlying etiology, clinical presentation, and treatment response. It is plausible that genetic factors contributing to alcohol dependence differ among these subgroups. Failing to account for this heterogeneity could dilute any potential genetic associations.

Gene-gene and gene-environment interactions: Alcohol dependence is a multifactorial condition influenced by interactions between various genes and environmental factors. The NET gene polymorphisms alone may not provide a complete picture of an individual's vulnerability to alcohol dependence. Considering these interactions is crucial to comprehensively understand the complex interplay between genetics and the environment.

Conclusion

The association between T-182C and G1287A polymorphisms in the norepinephrine transporter gene and alcohol dependence remains unsubstantiated. Recent well-powered studies and metaanalyses have consistently failed to demonstrate a significant association between these polymorphisms and alcohol dependence or its clinical subgroups. The complex nature of alcohol dependence suggests that multiple genetic and environmental factors contribute to its development and progression. Future research should focus on investigating other candidate genes and pathways involved in alcohol dependence to gain a deeper understanding of its genetic and potential therapeutic targets.