Table 1 Summary of candidate genes, polymorphisms, and their presumed effect on smoking cessation under the hypothesis that reduced dopaminergic neurotransmission is associated with lower likelihood to quit smoking.
Gene | Function of Gene Product | Polymorphism (Allele of interest) | Reported effects or associations of variant [reference] | Presumed effect on dopamine neuro-transmission | Expected direction of effect on smoking cessation among those with variant allele |
|---|---|---|---|---|---|
COMT | Dopamine metabolism | Val158Met (Met) | Met associated with low enzyme activity and thermolability [4] | Increase | more likely to quit smoking |
DRD2 | Dopamine receptor | -141C Ins/Del in promoter region (Del allele) | Lower promoter activity [1] | Decrease | less likely to quit smoking |
DRD2 | Dopamine receptor | Taq1 A at 10 kb downstream of coding sequence (A1 allele) | Reduced receptor binding [2, 3] | Decrease | less likely to quit smoking |
DRD3 | Dopamine receptor | Ser9Gly in N, terminal extracellular domain (Gly allele) | High dopamine binding affinity in Gly9 homozygotes [40] | Increase | more likely to quit smoking |
DRD4 | Dopamine receptor | (long repeat alleles: 6, 10 repeats) | 7-repeat alleles have decreased intracellular response to dopamine [41] | Decrease | less likely to quit smoking |
SLC6A3 | Dopamine reuptake | VNTR in 3' untranslated region (9-repeat allele) | 9-repeat alleles associated with lower levels of dopamine transporter expression [42] and lower brain protein levels [43] | Increase | more likely to quit smoking |
TH | Dopamine synthesis | TCAT, tetranucleotide VNTR first intron (10-repeat allele) | 10-repeat allele associated with reduced HVA levels (measure of dopamine metabolism) [44] | Decrease | less likely to quit smoking |