Interaction between blood lead concentration and δ-amino-levulinic acid dehydratase gene polymorphisms increases the odds of essential tremor

Elan D. Louis, LaKeisha Applegate, Joseph H. Graziano, Michael K. Parides, Vesna Slavkovich, Hari K. Bhat

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Blood lead (BPb) concentrations are elevated in essential tremor (ET) cases. The δ-amino-levulinic acid dehydratase (ALAD) gene codes for ALAD, the principal enzyme involved in lead kinetics. Carriers of the ALAD-2 allele may be more susceptible to lead toxicity. The objective of this study was to test, using a case-control design, whether an interaction between BPb concentration and ALAD allele status increases the odds of ET. Mean log BPb concentration was significantly higher in 63 cases than 101 controls (0.47 ± 0.26 vs. 0.35 ± 0.25 μg/dl). Eighteen (28.6%) cases vs. 17 (16.8%) controls had an ALAD-2 allele (OR = 1.98; 95% CI = 0.93-4.21). In an adjusted logistic regression analysis, the interaction term (ALAD allele status × log BPb concentration) was associated with increased odds for ET. In stratified analyses, log BPb concentration was not associated with odds of ET in individuals with two ALAD-I alleles (OR = 2.69; 95% CI = 0.61-11.82), but in individuals with an ALAD-2 allele, BPb concentration was significantly associated with odds of ET (OR = 80.29; 95% CI = 3.08-2,096.36). There was an interaction between BPb concentration and ALAD allele status; the odds of ET were greatly elevated in individuals with both an ALAD-2 allele and an elevated BPb concentration. The presence of increased circulating BPb concentrations along with a greater potential for lead toxicity (ALAD-2 allele) could result in greater cerebellar damage, thereby increasing the risk of developing tremor.

Original languageEnglish (US)
Pages (from-to)1170-1177
Number of pages8
JournalMovement Disorders
Volume20
Issue number9
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

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Hydro-Lyases
Essential Tremor
Alleles
Genes
levulinic acid
Lead
Tremor

Keywords

  • Epidemiology
  • Essential tremor
  • Etiology
  • Genetics
  • Lead

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Interaction between blood lead concentration and δ-amino-levulinic acid dehydratase gene polymorphisms increases the odds of essential tremor. / Louis, Elan D.; Applegate, LaKeisha; Graziano, Joseph H.; Parides, Michael K.; Slavkovich, Vesna; Bhat, Hari K.

In: Movement Disorders, Vol. 20, No. 9, 01.09.2005, p. 1170-1177.

Research output: Contribution to journalArticle

Louis, Elan D. ; Applegate, LaKeisha ; Graziano, Joseph H. ; Parides, Michael K. ; Slavkovich, Vesna ; Bhat, Hari K. / Interaction between blood lead concentration and δ-amino-levulinic acid dehydratase gene polymorphisms increases the odds of essential tremor. In: Movement Disorders. 2005 ; Vol. 20, No. 9. pp. 1170-1177.
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abstract = "Blood lead (BPb) concentrations are elevated in essential tremor (ET) cases. The δ-amino-levulinic acid dehydratase (ALAD) gene codes for ALAD, the principal enzyme involved in lead kinetics. Carriers of the ALAD-2 allele may be more susceptible to lead toxicity. The objective of this study was to test, using a case-control design, whether an interaction between BPb concentration and ALAD allele status increases the odds of ET. Mean log BPb concentration was significantly higher in 63 cases than 101 controls (0.47 ± 0.26 vs. 0.35 ± 0.25 μg/dl). Eighteen (28.6{\%}) cases vs. 17 (16.8{\%}) controls had an ALAD-2 allele (OR = 1.98; 95{\%} CI = 0.93-4.21). In an adjusted logistic regression analysis, the interaction term (ALAD allele status × log BPb concentration) was associated with increased odds for ET. In stratified analyses, log BPb concentration was not associated with odds of ET in individuals with two ALAD-I alleles (OR = 2.69; 95{\%} CI = 0.61-11.82), but in individuals with an ALAD-2 allele, BPb concentration was significantly associated with odds of ET (OR = 80.29; 95{\%} CI = 3.08-2,096.36). There was an interaction between BPb concentration and ALAD allele status; the odds of ET were greatly elevated in individuals with both an ALAD-2 allele and an elevated BPb concentration. The presence of increased circulating BPb concentrations along with a greater potential for lead toxicity (ALAD-2 allele) could result in greater cerebellar damage, thereby increasing the risk of developing tremor.",
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AB - Blood lead (BPb) concentrations are elevated in essential tremor (ET) cases. The δ-amino-levulinic acid dehydratase (ALAD) gene codes for ALAD, the principal enzyme involved in lead kinetics. Carriers of the ALAD-2 allele may be more susceptible to lead toxicity. The objective of this study was to test, using a case-control design, whether an interaction between BPb concentration and ALAD allele status increases the odds of ET. Mean log BPb concentration was significantly higher in 63 cases than 101 controls (0.47 ± 0.26 vs. 0.35 ± 0.25 μg/dl). Eighteen (28.6%) cases vs. 17 (16.8%) controls had an ALAD-2 allele (OR = 1.98; 95% CI = 0.93-4.21). In an adjusted logistic regression analysis, the interaction term (ALAD allele status × log BPb concentration) was associated with increased odds for ET. In stratified analyses, log BPb concentration was not associated with odds of ET in individuals with two ALAD-I alleles (OR = 2.69; 95% CI = 0.61-11.82), but in individuals with an ALAD-2 allele, BPb concentration was significantly associated with odds of ET (OR = 80.29; 95% CI = 3.08-2,096.36). There was an interaction between BPb concentration and ALAD allele status; the odds of ET were greatly elevated in individuals with both an ALAD-2 allele and an elevated BPb concentration. The presence of increased circulating BPb concentrations along with a greater potential for lead toxicity (ALAD-2 allele) could result in greater cerebellar damage, thereby increasing the risk of developing tremor.

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