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Angelika D. Wahner, PhD; Janet S. Sinsheimer, PhD; Jeff. M. Bronstein, MD, PhD; Beate Ritz, MD, PhD

Arch Neurol. 2007;64(6):836-840.

Background  The proinflammatory cytokines tumor necrosis factor (TNF-) and IL-1β (interleukin 1β) have a role in neuroinflammation, and functional polymorphisms in the TNF- and IL-1β genes may affect susceptibility to Parkinson disease (PD).

Objective  To investigate whether functional DNA polymorphisms of the TNF- and IL-1β 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-1β-511 and TNF--308.

Results  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--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.

Author Affiliations: Department of Epidemiology, UCLA School of Public Health (Drs Wahner and Ritz), and Departments of Biomathematics and Human Genetics (Dr Sinsheimer) and Neurology (Dr Bronstein), David Geffen School of Medicine at UCLA, University of California, Los Angeles, and Greater Los Angeles Veterans Administration Medical Center (Dr Bronstein), Los Angeles.

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