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.
Ton
Thanh G N
TG
Neuroepidemiology Group, University of Washington, Seattle, WA, USA. thanhton@u.washington.edu
Longstreth
W T
WT
Koepsell
Thomas D
TD
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