The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited

Cloé Domenighetti, Andreas Puschmann, Emil Ygland Rödström, Alexis Elbaz, Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) Consortium

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

BACKGROUND: Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions.

OBJECTIVE: To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction.

METHODS: We genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA-DRB1.

RESULTS: At the amino acid level, a valine at position 11 (V11) in HLA-DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59-0.93, PInteraction = 0.028). In silico predictions of the influence of V11 and smoking-induced modifications of α-synuclein on binding affinity showed findings consistent with this interaction pattern.

CONCLUSIONS: Despite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Originalspråkengelska
Sidor (från-till)1929-1937
TidskriftMovement Disorders
Volym37
Nummer9
Tidigt onlinedatum2022 juli 10
DOI
StatusPublished - 2022

Bibliografisk information

© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Ämnesklassifikation (UKÄ)

  • Genetik

Fingeravtryck

Utforska forskningsämnen för ”The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här