Table 1.

Gene polymorphisms under consideration and the literature summary.

Gene/Polymorphism	Number of Reference Sources	95% CI Overall Summary
Dopamine D1 Receptor (DRD1): rs4532—risk allele G	3	The genetic variation in DRD1 and its relationship to a predisposition to alcoholism have been supported by various studies. A statistically significant association of DRD1 rs4532 polymorphism with alcohol dependence was found among Indian males (90 cases vs. 122 controls). Other studies also demonstrated that this could be associated with the impulsivity and aggressiveness of AUD patients.
Dopamine D2 Receptor (DRD2): rs1800497—risk allele A1	118	From the meta-analysis of numerous case–control studies (total of 18,290 cases vs. 19,809 controls, including US Caucasian, native and African-American, British, French, Italian, Swedish, Finnish, Spanish, Mexican, Brazilian, Scandinavian, Japanese) pooled with the random effect models, the DRD2 rs1800497 was found to be associated with a risk of AUD and several AUD-related conditions.
Dopamine D3 Receptor (DRD3): rs6280—risk allele C (Ser9Gly)	3	Several case–control studies investigated the association between the DRD3 rs6280 polymorphism and alcohol dependence. In a Korean study (243 cases vs. 130 controls), the DRD3 rs6280 polymorphism was significantly associated with AUD development.
Dopamine D4 Receptor (DRD4): rs1800955—risk allele C (48bp repeat VNTR)	35	A meta-analysis of various case–control studies (total 2997 cases vs. 2588 controls, including US Caucasian, Mexican-American, Indian) pooled with the random effect models found that the DRD4 rs1800955 polymorphism was associated with the risk of developing AUD and AUD-related conditions.
Dopamine Transporter Receptor (DAT1): SLC6A3 3′-UTR—risk allele A9 (40bp repeat VNTR)	43	The central dopaminergic reward pathway is likely involved in alcohol intake and the progression of alcohol dependence. DAT1 is a primary mediator of dopaminergic neurotransmission. From the meta-analysis of numerous case–control studies (total 3790 cases vs. 3446 controls) pooled with the random effect models, the DAT1 SLC6A3 3′-UTR risk allele was found to be marginally associated with a risk of AUD and/AUD-related conditions.
Catechol-O-Methyltransferase (COMT): rs4680—risk allele G (Val158Met)	13	A plethora of evidence supports COMT as a candidate gene that likely contributes to schizophrenia and substance use disorder. A meta-analysis of several case–control studies (total of 1212 cases vs. 933 controls, including US Caucasian, Finnish, Croatian, and Taiwanese) pooled with a random effect model, the association of COMPT rs4680 polymorphism with the risk of AUD and AUD-related conditions was found to have marginal statistical significance.
µ-Opioid Receptor (OPRM1): rs1799971—risk allele G (A118G)	28	Opioid receptors play an essential role in ethanol reinforcement and alcohol dependence risk. Some features of alcohol dependence are likely associated with polymorphisms of the OPRM1 gene expressing µ-opioid receptors. From the meta-analysis of case–control studies (total of 3096 cases vs. 2896 controls, including US Caucasian, Spanish, Turkish, and Asian) pooled with the random effect model, the results indicated that the association of a functional OPRM variant and the risk of alcohol dependence was found to have marginal statistical significance.
γ-Aminobutyric Acid (GABA) A Receptor, β-3 Subunit (GABRB3): CA repeat—risk allele 181	6	The GABAergic system has been implicated in alcohol-related behaviors. From case–control studies (171 cases vs. 45 controls), the association of variants of the GABRB3 gene with alcohol dependence is, however, inconclusive. A more extensive controlled study is required for improved results.
Monoamine Oxidase A (MAO-A): 3′ 30bp VNTR -risk allele 4R DNRP	6	The function of monoamine oxidase (MAO) in alcoholism was determined using several case–control studies (170 cases vs. 177 controls). Although genetic heterogeneity is suspected of underlying alcoholism and MAO-A mutations may play a role in susceptibility to alcoholism, the overall results were not found to be statistically significant. A more extensive controlled study is required to obtain conclusive results.
Serotonin Transporter Receptor (5HTT) Linked Promoter Region (5HTTLPR) in SLC6A4: rs25531—risk allele S′	20	Serotonin (5-HT) has been demonstrated to regulate alcohol consumption. Since the activity of the 5-HT transporter protein (5-HTT) regulates 5-HT levels, it may contribute to the risk of alcohol dependence. From the meta-analysis of some case–control studies (total 9996 cases vs. 9950 controls) pooled with the random effect models, the association between alcohol dependence and a polymorphism in the 5-HTTLPR was significant.