Interaction of Smoking and Genetic Polymorphisms in the Dopaminergic Pathway in Relation to Parkinson’s Disease: A Scoping Review

The inverse association of Parkinson's disease (PD) and smoking has been well established, but it is rarely investigated in the context of the different genetic backgrounds of the patients. This scoping review aims to comprehensively review the literature on the interactions of different essential genes involved in the dopaminergic pathway with smoking and how they modulate the risk of PD with smoking. A search using the keywords and abbreviations of smoking, genetic polymorphism, and parkinsonism was conducted in Web of Science, PubMed, Cochrane, and Scopus databases. References were retrieved and screened by two authors independently. Eleven human studies were included with 5131 cases and 7542 control adult populations with a male predominance (>60%) and multiethnic groups, mainly European origin populations. Most gene polymorphisms showed no modulation of the smoking-PD risk. Nevertheless, the risk was shown to change with MAO-B rs1799836 gene polymorphism in three studies where the G allele was associated with smoking protection against PD in 16.5% and 13.14% of cases and controls, respectively. While the COMT rs4680 polymorphism was suggested to interact with smoking in one study with 238 (37.9%) cases and 369 (31.5%) controls (p-value = 0.061), the effect of smoking on PD risk varied significantly with different SV2C (rs30196 and rs10214163) genotypes. Our study revealed the complexity of genetic polymorphism in the smoking-PD relationship. This explores the possibility of further research with larger sample sizes, accounting for different ethnic groups, to establish definitive links that can aid in treatment and prevention strategies.