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Pooled analysis of the HLA‐DRB1 by smoking interaction in Parkinson disease
Author(s) -
Chuang YuHsuan,
Lee PeiChen,
Vlaar Tim,
Mulot Claire,
Loriot MarieAnne,
Hansen Johnni,
Lill Christina M.,
Ritz Beate,
Elbaz Alexis
Publication year - 2017
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25065
Subject(s) - odds ratio , medicine , logistic regression , human leukocyte antigen , disease , confounding , population , parkinson's disease , genotyping , demography , immunology , genotype , genetics , antigen , biology , gene , environmental health , sociology
Objective Inflammatory response plays an important role in Parkinson disease (PD). Previous studies have reported an association between 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. We performed a pooled analysis of the interaction between HLA‐DRB1 and smoking in PD in 3 population‐based case–control studies from Denmark and France. Methods We included 2,056 cases and 2,723 controls from 3 PD studies (Denmark, France) that obtained information on smoking through interviews. Genotyping of the rs660895 polymorphism in the HLA‐DRB1 region was based on saliva or blood DNA samples. To assess interactions, we used logistic regression with product terms between rs660895 and smoking. We performed random‐effects meta‐analysis of marginal associations and interactions. Results Both 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. A multiplicative interaction was observed between rs660895 and smoking using codominant, additive (interaction parameter = 1.37, p = 0.005), and dominant (interaction parameter = 1.54, p = 0.001) genetic models without any heterogeneity ( I ² = 0.0%); the inverse association of rs660895‐(AG+GG) with PD seen in never smokers (OR = 0.64, p < 0.001) disappeared among ever smokers (OR = 1.00, p = 0.99). Similar interactions were observed when we investigated light and heavy smokers separately. Interpretation 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. Ann Neurol 2017;82:655–664