To explore the published studies evaluating the interaction between dopamine receptor polymorphism and smoking and its effect on PD risks.

Parkinson’s disease (PD) is known for the evident decrease in striatal dopamine concentrations accompanied by a rise in the densities of dopaminergic receptors. Smoking was associated with reduced risks of PD. Dopamine receptor polymorphisms have been associated with certain smoking behaviours among populations. Within the context of PD, some studies suggested an interaction between genetic polymorphisms and smoking on PD risks. 

Using the relevant keywords, a systematic search of PubMed, Scopus, Web of Science, and Cochrane databases was conducted until September 2024. The results were screened by two authors independently, and a third author resolved the conflicts. We extracted data on patients’ demographics (age, gender, ethnicity), methodological design, genes and variants, and the main results and conclusions of the study. 

We included five case-control studies including 2668 PD cases and 4260 control participants (55.32% and 57.22% males). Three studies included only Caucasians, non-Hispanic whites comprised most of another study, while one study did not specify the ethnic groups. The studies included variants of DRD2, DRD3, and DRD4 genes. DRD2 Taq1 A was the most commonly studied in four studies and DRD2 Taq1 B was studied in two. The inverse relationship between smoking and PD was found in all articles. Notably, all studies failed to reveal any modification of the tested genetic polymorphism on the smoking effect on PD risk. Regardless of ethnic groups or gender, the inverse smoking-PD relationship did not change with changes in the mentioned gene variants although some comparisons might be imprecise due to low numbers of some ethnic groups. 

Despite the scarcity of literature, DRD polymorphisms do not appear to modulate or interact with smoking effects on PD. Further extensive studies are needed.