Title: Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease.
Authors: Wahner, Angelika D; Sinsheimer, Janet S; Bronstein, Jeff M; Ritz, Beate
Published In Arch Neurol, (2007 Jun)
Abstract: 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).To investigate whether functional DNA polymorphisms of the TNF-alpha and IL-1beta 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.Genotypes of IL-1beta-511 and TNF-alpha-308.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).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.
PubMed ID: 17562931
MeSH Terms: Aged; Case-Control Studies; Female; Gene Dosage; Genetic Predisposition to Disease*; Genetic Variation; Genotype; Heterozygote; Homozygote; Humans; Interleukin-1alpha/genetics*; Male; Middle Aged; Parkinson Disease/genetics*; Polymorphism, Genetic*; Tumor Necrosis Factor-alpha/genetics*