Genetic variants in nicotinic receptors and smoking cessation in Parkinson's disease

Negative associations between smoking and Parkinson's disease (PD) are well documented. While common biases may not explain this association, some studies have suggested reverse causality and ease of quitting might be an early sign of PD, possibly related to a reduced nicotinic response. We investigated nicotinic receptor (nAChR) genetics to add to our understanding of possible biologic mechanisms underlying the smoking-PD relationship.

We relied on 612 patients and 691 controls enrolled in the PEG (Parkinson's Environment and Gene) study for whom we obtained information on smoking and quitting ease through interviews. Genotyping in the nAChR genes, i.e. CHRNA5-A3-B4 and CHRNB3-A6 gene regions that have been linked to smoking or quitting behaviors, were based on blood and saliva DNA samples. We assessed associations with logistic regression assuming logit-additive allelic effects and used product terms for genetic allele status and smoking or quitting assessing interactions.

As expected, we observed negative associations between smoking and PD that were strongest for current followed by former smokers. In former smokers, high quitting difficulty was negatively associated with PD risk (extremely hard vs. easy: OR = 0.62 [0.39-0.99], p = 0.05), meaning those who developed PD were able to quit smoking with less difficulty than controls. The CHRNA3 rs578776-A allele predicted quitting difficulty in smoking controls (OR = 0.53 [0.32-0.91], p = 0.02), but not in smoking PD patients (OR = 1.09 [0.61-1.95], p = 0.77).

Our study further corroborates previous findings that ease of quitting may be an early sign of PD onset related to a loss of nicotinic response in prodromal stages.