Objective: To investigate interactions between HLA-DRB1 rs660895 polymorphisms and smoking in PD using meta-analysis to pool data from three large population-based studies.

Background: Inflammatory response plays an important role in Parkinson’s disease (PD). Previous studies have reported an association between the human leukocyte antigen (HLA)-DRB1 and the risk of PD. There has also been growing interest in investigating whether inflammation-related genes interact with environmental factors such as smoking to influence PD risk.

Methods: We included 2,073 cases and 2,756 controls from PD studies in Denmark and France that obtained information on smoking through interviews. Genotyping was based on saliva or blood DNA samples. To assess interactions, we used logistic regressions with product terms of rs660895 and smoking variables. Random-effects meta-analysis of marginal associations and interactions were performed in the STATA package metan.

Results: In the meta-analysis, rs660895 variant genotypes were significantly associated with a decreased risk of PD (AG vs. AA: OR= 0.82; GG vs. AA: OR= 0.55). A sub-multiplicative interaction was found between rs660895 and smoking in both codominant and dominant genetic models (OR interaction=1.54, p=0.001), and the protective effect of the rs660895 variant on PD was lost. When separating light from heavy smokers, similar interaction effects were estimated.

Conclusions: Our study provides the first evidence that smoking modifies the previously reported protective effect of rs660895 polymorphisms on the risk of PD. The protective effect of the rs660895 G allele is only apparent in non-smokers.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/meta-analysis-of-the-interaction-between-hla-drb1-and-smoking-with-parkinsons-disease/