Environmental toxins and risk of narcolepsy among people with HLA DQB1*0602.
One etiologic model for narcolepsy suggests that some environmental toxin selectively and irreversibly destroys hypocretin-producing cells in individuals with human leukocyte antigen (HLA) DQB1(*)0602. Between 2001 and 2005, the authors conducted a population-based case-control study in King County, Washington to examine narcolepsy risk in relation to toxins found in jobs, hobbies, and other non-vocational activities. Sixty-seven cases and 95 controls were enrolled; all were between ages 18 and 50 and positive for HLA DQB1(*)0602. All were administered in-person interviews about jobs, hobbies or other non-vocational activities before age 21. All analyses were adjusted for African-American race and income. Risk increased significantly for jobs involving heavy metals (odds ratio [OR]=4.7; 95% confidence interval [CI]: 1.5, 14.5) and for highest levels of exposure to woodwork (OR: 3.0; 95% CI: 1.0, 8.9), fertilizer (OR=3.1; 95% CI: 1.1, 9.1), and bug or weed killer (OR=4.5; 95% CI: 1.5, 13.4). Associations were of borderline significance for activities involving ceramics, pesticides, and painting projects. Significant dose-response relationships were evident for jobs involving metals (p<0.03), paints (p<0.03), and bug or weed killer (p<0.02). Additional studies are needed to replicate these findings and continue the search for specific toxins that could damage hypocretin neurons in genetically susceptible people.
Neuroepidemiology Group, University of Washington, Seattle, WA, USA. thanhton@u.washington.edu
Thanh G N
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Ton
W T
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Longstreth
Thomas D
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Koepsell
D000293:Adolescent; D000328:Adult; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis* / Q000706:statistics & numerical data; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006683:HLA-DQ Antigens / Q000378:metabolism*; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D019216:Metals, Heavy / Q000633:toxicity; D008875:Middle Aged; D009290:Narcolepsy / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D010575:Pesticides / Q000633:toxicity; D012306:Risk; D014861:Washington; D055815:Young Adult
D004785:Environmental Pollutants; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D008562:Membrane Glycoproteins; D019216:Metals, Heavy; D010575:Pesticides