Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Association between blood lead and the risk of amyotrophic lateral sclerosis. 2040 59

Blood lead and bone turnover may be associated with the risk of amyotrophic lateral sclerosis (ALS). We aimed to assess whether these factors were also associated with time from ALS diagnosis to death through a survival analysis of 145 ALS patients enrolled during 2007 in the National Registry of Veterans with ALS. Associations of survival time with blood lead and plasma biomarkers of bone resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay, site of onset, and score on the Revised ALS Functional Rating Scale. Hazard ratios were calculated for each doubling of biomarker concentration. Blood lead, plasma CTX, and plasma PINP were mutually adjusted for one another. Increased lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival, whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42, 0.83), after ALS diagnosis. No interactions were observed between lead or bone turnover and other prognostic indicators. Lead toxicity and bone metabolism may be involved in ALS pathophysiology.
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PMID:Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis. 2902 Jan 33