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

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.