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Smoking Alters Genetic Relationship with Parkinson’s

Smoking, HLA-DRB1 may be involved in common pathways, possibly neuroinflammation

MONDAY, Oct. 23, 2017 (HealthDay News) — Smoking may modify a previously reported genetic association with Parkinson’s disease (PD), according to an analysis published online Oct. 5 in the Annals of Neurology.

Yu-Hsuan Chuang, M.P.H., from the University of California, Los Angeles, and colleagues conducted a pooled analysis of the interaction between HLA-DRB1 and smoking in PD in three population-based case-control studies from Denmark and France involving 2,056 cases and 2,723 controls. Genotyping of the rs660895 polymorphism in the HLA-DRB1 region was based on blood or saliva DNA samples.

The researchers found that carrying rs660895-G (AG vs. AA: odds ratio [OR], 0.81; GG vs. AA: OR, 0.56; P-trend = 0.003) and ever smoking (OR, 0.56; P < 0.001) were inversely associated with PD. There was a multiplicative interaction between rs660895 and smoking using codominant, additive (P = 0.005), and dominant (P = 0.001) genetic models without any heterogeneity. An inverse association of rs660895-(AG+GG) and PD in never smokers (OR, 0.64; P < 0.001) disappeared among ever smokers (OR, 1; P = 0.99). Similar interactions were noted when light and heavy smokers were investigated separately.

“Our study provides the first evidence that smoking modifies the previously reported inverse association of rs660895-G with PD, and suggests that smoking and HLA-DRB1 are involved in common pathways, possibly related to neuroinflammation,” conclude the authors.

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