The proinflammatory cytokines tumor necrosis factor α (TNF-α) and IL-1β (interleukin 1β) have a role in neuroinflammation, and functional polymorphisms in the TNF-α and IL-1β genes may affect susceptibility to Parkinson disease (PD).
To investigate whether functional DNA polymorphisms of the TNF-α and IL-1β genes affect the risk of PD.
Population-based case-control study.
Three rural California counties (Fresno, Tulare, and Kern).
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-1β-511 and TNF-α-308.
We observed a greater than 2-fold increased risk of PD among carriers of the homozygous variant genotype of IL-1β-511 (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.27-4.02) and the homozygous variant genotype of TNF-α-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).
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.