Table 3.

GARS is based on the following genes linked to hypodopaminergia.

Gene	Polymorphism	Location	Risk Allele	Function Linked to Hypodopaminergia	Reference
DRD1	rs4531 or rs4532	Chr −5	A	rs4532 is known to reduce the function of the DRD1 gene, which is needed as a “go” drive to activate D1 receptors causing normal dopamine function.	Batel et al. (2008) [15].
DRD2	rs1800497	Chr-11	A	rs1800497 equates functionally to 30–40% lower density of dopamine D2 receptors resulting hypodopaminergic function	Noble et al (1991) [8].
DRD3	rs6280	Chr3	C	Rs6280 in D3 causes an imbalance of the DRD3 function and has assiciated with Heroin Dependence.	Kuo et al. (2014) [16].
DRD4	48 base repeat VNTR	Chr 11 exon 3	Above 7 R	Similar to the D2, the VNTR 7 R and above results in a hypodopaminergia due to lower receptor function.	Van Tol (1998) [17]
COMT	rs4680	Chr 22	G	Carrying the 9 R allele leads to a high activity of catabolism of dopamine in synapse inducing a hypodopaminergia in the synapse.	Isir et al. (2008) [18] and Wichers et al. [19]
OPRM1	rs1799971	Chr 6	G	The G allele is the risk variant of the MOR 118A>G (p.Asn40Asp; SNP rs1799971) promotes a low dopamine function because there will be a lack of inhibition via the GABA inhibitory control of dopamine release at the reward site Nucleus Accumbens (NAc) inducing hypodopaminergia.	Ray et al. (2011) [20]
DAT1	40 base repeat VNTR	Chr 5 exon 15	9R	Carrying the 9 R allele leads to a high activity inducing a hypodopaminergia in the synapse. The DAT1 clears excess dopamine released from the pre-neuron into the synapse and prevents uptake into the receptors on the next neuron.	Byerley et al. (1993) [21].
MOA-A	30 base repeat VNTR	Chr X Promotor	3.5 R, 4R	The 3.5 R and 4 R variants are more active than 3 R or 5 R. Excessive amounts of dopamine are broken down in the presynaptic neuron which may result is less dopamine availability for release into the synaptic cleft arriers of the 3.5 and 4 R may display hypodopaminergia (low dopamine function).	Contini et al. (2006) [22].
5HTTLPR	43 base repeat INDEL/VNTR plus rs 25531	Chr 17	LG, S	The risk variant has 43 base -pair 5″ insertion/deletion, S′ at SNP rs25531. The long allele results in higher serotonin transporter mRNA transcription in human cell lines., The result is that Serotonin is highly reabsorbed from the synapse into the pre-nerve cell causing low serotonin content in the synapse leading to reduced function.	Merenakk et al. (2011) [23] and van der Zwaluw et al. (2010) [24].
GABRB3	CA repeat DNR	Chr 15 (downstream)	181	GABRA3 gene and the risk variant is CA-repeat, whereby allele 181 results in higher activity. This risk allele if overexpressed will cause low dopamine function hypodopaminergia leading to SUD because of inhibition of dopamine release at reward site	Namkoong et al. (2008) [25].