PMID- 28981958
OWN - NLM
STAT- MEDLINE
DCOM- 20171222
LR  - 20181113
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 82
IP  - 5
DP  - 2017 Nov
TI  - Pooled analysis of the HLA-DRB1 by smoking interaction in Parkinson disease.
PG  - 655-664
LID - 10.1002/ana.25065 [doi]
AB  - 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.
CI  - (c) 2017 American Neurological Association.
FAU - Chuang, Yu-Hsuan
AU  - Chuang YH
AD  - Department of Epidemiology, Fielding School of Public Health, University of 
      California, Los Angeles, Los Angeles, CA.
FAU - Lee, Pei-Chen
AU  - Lee PC
AD  - Department of Health Care Management, College of Health Technology, National 
      Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
FAU - Vlaar, Tim
AU  - Vlaar T
AD  - Universite Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
FAU - Mulot, Claire
AU  - Mulot C
AD  - INSERM UMR-S 1147, CRB EPIGENETEC, Univ. Paris Descartes, Sorbonne Paris Cite, 
      75006 Paris, France.
FAU - Loriot, Marie-Anne
AU  - Loriot MA
AD  - Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, 
      Biochimie, Pharmacogenetique et Oncologie Moleculaire, 75015 Paris, France.
FAU - Hansen, Johnni
AU  - Hansen J
AD  - Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, 
      Denmark.
FAU - Lill, Christina M
AU  - Lill CM
AD  - Genetic and Molecular Epidemiology Group, Institute of Neurogenetics, University 
      of Lubeck, Lubeck, Germany.
FAU - Ritz, Beate
AU  - Ritz B
AD  - Department of Epidemiology, Fielding School of Public Health, University of 
      California, Los Angeles, Los Angeles, CA.
AD  - Department of Neurology, School of Medicine, University of California, Los 
      Angeles, Los Angeles, CA.
AD  - Department of Environmental Health Sciences, Fielding School of Public Health, 
      University of California, Los Angeles, Los Angeles, CA.
FAU - Elbaz, Alexis
AU  - Elbaz A
AD  - Universite Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
LA  - eng
GR  - R01 ES013717/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20171026
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Aged
MH  - Case-Control Studies
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Male
MH  - Models, Genetic
MH  - Parkinson Disease/*genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Smoking/*genetics
PMC - PMC5798887
MID - NIHMS911244
COIS- Potential Conflicts of Interest: Nothing to report.
EDAT- 2017/10/06 06:00
MHDA- 2017/12/23 06:00
PMCR- 2018/11/01
CRDT- 2017/10/06 06:00
PHST- 2017/05/24 00:00 [received]
PHST- 2017/10/02 00:00 [revised]
PHST- 2017/10/04 00:00 [accepted]
PHST- 2017/10/06 06:00 [pubmed]
PHST- 2017/12/23 06:00 [medline]
PHST- 2017/10/06 06:00 [entrez]
PHST- 2018/11/01 00:00 [pmc-release]
AID - 10.1002/ana.25065 [doi]
PST - ppublish
SO  - Ann Neurol. 2017 Nov;82(5):655-664. doi: 10.1002/ana.25065. Epub 2017 Oct 26.