Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease

Background: The proinflammatory cytokines tumor necrosis factor alpha ( TNF-alpha) and IL-1 beta ( interleukin 1 beta) have a role in neuroinflammation, and functional polymorphisms in the TNF-alpha and IL-1 beta genes may affect susceptibility to Parkinson disease ( PD). Objective: To investigate whether functional DNA polymorphisms of the TNF-alpha and IL-1 beta 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-1 beta-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-1 beta-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.