Amyotrophic Lateral Sclerosis, Lead, and Genetic Susceptibility: Polymorphisms in the -Aminolevulinic Acid Dehydratase and Vitamin D Receptor Genes Freya Kamel,1 David M. Umbach,1 Teresa A. Lehman,2 Lawrence P. Park,3 Theodore L. Munsat,4 Jeremy M. Shefner,5 Dale P. Sandler,1 Howard Hu,6 and Jack A. Taylor1
1National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA; 2Bioserve Biotechnologies, Rockville, Maryland, USA; 3Westat, Durham, North Carolina, USA; 4New England Medical Center, Boston, Massachusetts, USA; 5SUNY Upstate Medical University, Syracuse, New York, USA 6Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts, USA
Abstract Previous studies have suggested that lead exposure may be associated with increased risk of amyotrophic lateral sclerosis (ALS) . Polymorphisms in the genes for -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. Key words: -aminolevulinic acid dehydratase, amyotrophic lateral sclerosis, genetic susceptibility, lead, vitamin D receptor. Environ Health Perspect 111:1335-1339 (2003) . doi:10.1289/ehp.6109 available via http://dx.doi.org/ [Online 1 April 2003] The full version of this article is available for free in HTML or PDF formats. |