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Updated: Jul 14, 2026

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease
Angelika D Wahner1, Janet S Sinsheimer, Jeff M Bronstein
1Department of Epidemiology, UCLA School of Public Health, University of California, Los Angeles, CA 90095-1772, USA. awahner@ucla.edu
Background:
The proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and IL-1beta (interleukin 1beta) have a role in neuroinflammation, and functional polymorphisms in the TNF-alpha and IL-1beta genes may affect susceptibility to Parkinson disease (PD).
Objective:
To investigate whether functional DNA polymorphisms of the TNF-alpha and IL-1beta genes affect the risk of PD.
Design:
Population-based case-control study.
Setting:
Three rural California counties (Fresno, Tulare, and Kern).
Participants:
Two hundred eighty-nine incident idiopathic PD cases and 269 population control subjects, marginally matched by age, sex, and race/ethnicity.
Main Outcome Measures:
Genotypes of IL-1beta-511 and TNF-alpha-308.
Results:
We observed a greater than 2-fold increased risk of PD among carriers of the homozygous variant genotype of IL-1beta-511 (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.27-4.02) and the homozygous variant genotype of TNF-alpha-308 (OR, 2.49; 95% CI, 0.90-6.85) and an almost 3-fold increased risk among carriers of the homozygous variant genotype for either or both polymorphisms (OR, 2.92; 95% CI, 1.66-5.16).
Conclusions:
A smaller magnitude of PD risk increase among carriers of the heterozygous genotype for either or both polymorphisms suggests a gene-dosing effect (OR, 1.45; 95% CI, 0.97-2.16; P<.001 for trend). Results were not sensitive to exclusion of all nonwhite subjects or to adjustment for nonsteroidal anti-inflammatory drug use or smoking.
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