Amyotrophic Lateral Sclerosis, Lead, and Genetic Susceptibility: Polymorphisms in the Delta-Aminolevulinic Acid Dehydratase and Vitamin D Receptor Genes

Details

• Personal Author:
  Hu H ; Kamel F ; Lehman TA ; Munsat TL ; Park LP ; Sandler DP ; Shefner JM ; Taylor JA ; Umbach DM
• Description:
  Previous studies have suggested that lead exposure may be associated with increased risk of amyotrophic lateral sclerosis (ALS). Polymorphisms in the genes for delta-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) may affect susceptibility to lead exposure. We used data from a case-control study conducted in New England from 1993 to 1996 to evaluate the relationship of ALS to polymorphisms in ALAD and VDR and the effect of these polymorphisms on the association of ALS with lead exposure. The ALAD 2 allele (177G to C; K59N) was associated with decreased lead levels in both patella and tibia, although not in blood, and with an imprecise increase in ALS risk [odds ratio (OR) = 1.9; 95% confidence interval (95% CI), 0.60-6.3]. We found a previously unreported polymorphism in ALAD at an Msp1 site in intron 2 (IVS2+299G>A) that was associated with decreased bone lead levels and with an imprecise decrease in ALS risk (OR = 0.35; 95% CI, 0.10-1.2). The VDR B allele was not associated with lead levels or ALS risk. Our ability to observe effects of genotype on associations of ALS with occupational exposure to lead or with blood or bone lead levels was limited. These findings suggest that genetic susceptibility conferred by polymorphisms in ALAD may affect ALS risk, possibly through a mechanism related to internal lead exposure. [Description provided by NIOSH]
• Subjects:
  Blood Demography Environmental Exposure Genetics Lead Occupational Health Risk Assessment Risk Factors Safety Surveys And Questionnaires
• Keywords:
  Bone Structure Case Control Studies Demographic Characteristics Deoxyribonucleic Acids DNA Exposure Levels Genes Genotype Health Effects Humans Lead Compounds Questionnaires Risk Factors Statistical Analysis

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• ISSN:
  0091-6765
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; North Carolina ; OSHA Region 1 ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  111
• Issue:
  10
• NIOSHTIC Number:
  nn:20057246
• Citation:
  Environ Health Perspect 2003 Aug; 111(10):1335-1339
• Contact Point Address:
  F. Kamel, Epidemiology Branch, National Institute of Environmental Health Sciences, Box 12233, MD A3-05, Research Triangle Park, NC 27709
• Email:
  kamel@niehs.nih.gov
• CAS Registry Number:
  Lead (CAS RN 7439-92-1)
• Federal Fiscal Year:
  2003
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20030701
• Source Full Name:
  Environmental Health Perspectives
• End Date:
  20050630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:98da76bdd1193b48aace2c498f2206221c5bb21c230b59bede326d25025709491f75273c788a025215f13ad41a57b4c0f5b7ad2406bf1eb9cb05b579bcab223d
• Download URL:
  https://stacks.cdc.gov/view/cdc/214663/cdc_214663_DS1.pdf
• File Type:
  [PDF - 147.22 KB ]