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.


METHODS
Population-based case-control study.


METHODS
Three rural California counties (Fresno, Tulare, and Kern).


METHODS
Two hundred eighty-nine incident idiopathic PD cases and 269 population control subjects, marginally matched by age, sex, and race/ethnicity.


METHODS
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.
Wahner
Angelika D
AD
Department of Epidemiology, UCLA School of Public Health, University of California, Los Angeles, CA 90095-1772, USA. awahner@ucla.edu
Sinsheimer
Janet S
JS
Bronstein
Jeff M
JM
Ritz
Beate
B
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D053582:Interleukin-1alpha; D014409:Tumor Necrosis Factor-alpha