Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease.

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.