title: Association between blood lead and the risk of amyotrophic lateral sclerosis.
abstract: The authors conducted a 2003-2007 case-control study including 184 cases and 194 controls to examine the association between blood lead and the risk of amyotrophic lateral sclerosis (ALS) among US veterans and to explore the influence on this association of bone turnover and genetic factors related to lead toxicokinetics. Blood lead, plasma biomarkers of bone formation (procollagen type 1 amino-terminal peptide (PINP)) and resorption (C-terminal telopeptides of type 1 collagen (CTX)), and the K59N polymorphism in the delta-aminolevulinic acid dehydratase gene, ALAD, were measured. Odds ratios and 95% confidence intervals for the association of blood lead with ALS were estimated with unconditional logistic regression after adjustment for age and bone turnover. Blood lead levels were higher among cases compared with controls (P < 0.0001, age adjusted). A doubling of blood lead was associated with a 1.9-fold increased risk of ALS (95% confidence interval: 1.3, 2.7) after adjustment for age and CTX. Additional adjustment for PINP did not alter the results. Significant lead-ALS associations were observed in substrata of PINP and CTX levels. The K59N polymorphism in the ALAD gene did not modify the lead-ALS association (P = 0.32). These results extend earlier findings by accounting for bone turnover in confirming the association between elevated blood lead level and higher risk of ALS.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Lydia C
authors.initials: LC
authors.lastname: Kwee
authors.forename: Kelli D
authors.initials: KD
authors.lastname: Allen
authors.forename: David M
authors.initials: DM
authors.lastname: Umbach
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.forename: Mary
authors.initials: M
authors.lastname: Watson
authors.forename: Jean
authors.initials: J
authors.lastname: Keller
authors.forename: Eugene Z
authors.initials: EZ
authors.lastname: Oddone
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.forename: Silke
authors.initials: S
authors.lastname: Schmidt
authors.forename: Freya
authors.initials: F
authors.lastname: Kamel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D015415:Biomarkers; D001862:Bone Resorption / Q000150:complications / Q000453:epidemiology; D001842:Bone and Bones / Q000378:metabolism; D016022:Case-Control Studies; D016001:Confidence Intervals; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007854:Lead / Q000097:blood*; D007855:Lead Poisoning / Q000097:blood / Q000150:complications; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010012:Osteogenesis; D000623:Porphobilinogen Synthase / Q000235:genetics; D012042:Registries; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D014728:Veterans / Q000706:statistics & numerical data
chemical_list: D015415:Biomarkers; D007854:Lead; D000623:Porphobilinogen Synthase
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