Article

Association Between Blood Lead and the Risk of Amyotrophic Lateral Sclerosis

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
American journal of epidemiology (Impact Factor: 5.23). 05/2010; 171(10):1126-33. DOI: 10.1093/aje/kwq063
Source: PubMed

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 δ-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.

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    • "Among the metals analyzed, Pb resulted higher in patients' than in controls' group. Much evidence in the literature describes Pb as a neurotoxic agent and as being related to ALS[22,23], since high levels of this metal have been found both in blood and in cerebrospinal fluid of ALS patients[24,25]. In our analyses, Pb levels were twice higher in ALS subjects than in controls, supporting the hypothesis of a possible involvement of this metal in the etiology of the disease. "
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    ABSTRACT: Amyotrophic Lateral Sclerosis (ALS) has often been associated with improper/altered metal metabolism. Analysis of thiophylic metals in serum from a small and geographically restricted cohort of ALS patients indicates contents of Pb and Ni much higher in patients than in controls (Ni, 5-fold; Pb, 2-fold). Se levels are also higher in the patients’ group, which has instead lower As levels than controls. Thiophylic metals may impair biogenesis of FeS clusters or substitute for iron, even in folded proteins; Se may non-functionally replace S. Thus, improper assembly/ function of FeS proteins could represent another possible issue to be considered in ALS pathogenesis.
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    • "Multiple lines of evidence suggest that lead exposure plays a significant role in the aetiology of MND. These lines of evidence include the meta-analysis between MND and occupational lead exposure[11], previous bone lead studies23242526and studies that have found positive associations between MND and lead in human biological samples[13,14,16], questionnaires[12,202122and the results from this study. Lead is also known to cause oxidative stress[69,70]. "
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    ABSTRACT: Background: The age standardised death rate from motor neuron disease (MND) has increased from 1.29 to 2.74 per 100,000, an increase of 112.4% between 1959 and 2013. It is clear that genetics could not have played a causal role in the increased rate of MND deaths over such a short time span. We postulate that environmental factors are responsible for this rate increase. We focus on lead additives in Australian petrol as a possible contributing environmental factor. Methods: The associations between historical petrol lead emissions and MND death trends in Australia between 1962 and 2013 were examined using linear regressions. Results: Regression results indicate best fit correlations between a 20 year lag of petrol lead emissions and age-standardised female death rate (R² = 0.86, p = 4.88 × 10(-23)), male age standardised death rate (R² = 0.86, p = 9.4 × 10(-23)) and percent all cause death attributed to MND (R² = 0.98, p = 2.6 × 10(-44)). Conclusion: Legacy petrol lead emissions are associated with increased MND death trends in Australia. Further examination of the 20 year lag between exposure to petrol lead and the onset of MND is warranted.
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    • "It is possible that exposure to occupational or environmental Pb can be the triggering pathogen in genetically susceptible individuals as described in a human casereport [64]. In a case–control study, results suggested the association between elevated blood Pb level and the higher risk of ALS in patients, by accounting for bone turnover [28]. Moreover, there is evidence that some polymorphisms in the genes for δ-aminolevulinic acid dehydratase (ALAD) resulted significantly associated with bone Pb levels in ALS patients compared with controls and may affect the ALS risk [42]. "
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    ABSTRACT: The association between exposure to toxic metals and amyotrophic lateral sclerosis (ALS) was explored in a population-based case-control study in the Sardinia island (Italy), a region characterized by elevated rates of ALS cases. In 34 patients with ALS (mean age, 62±10years) and 30 controls (mean age, 65±11years), Al, Cd, Hg, Mn and Pb were determined in blood, hair and urine by sector field inductively coupled mass spectrometry. Results indicated that, in blood, concentrations of Al (p=0.045) and Pb were higher (p=0.026) in ALS patients than in control subjects. In hair, a depletion of Al (p=0.006) and Mn (p=0.032) concentrations in ALS subjects respect to controls was found. In urine, no significant differences between cases and controls were observed. Thus, some metals seemed to be associated with ALS degeneration, but a definitive conclusion is still far considering the multiple risk factors (genetic mutations, environmental toxicants and stressors) involved in the disease. Finally, the interpretation that deregulated metal concentrations can be a consequence of the degenerative process, rather than a cause, is also valid.
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