title: Delta-amino-levulinic acid dehydratase gene and essential tremor.
abstract: BACKGROUND
  Several reports found a relationship between increased serum lead levels and the risk for essential tremor (ET), especially in carriers of the minor allele of the single nucleotide polymorphism (SNP) rs1800435 in the aminolevulinate dehydratase (ALAD) gene, which is involved in the synthesis of haem groups. Our group reported decreased risk for ET in carriers of the minor alleles of the rs2071746 and rs1051308 SNPs in the haem-oxygenases 1 and 2 (HMOX1 and HMOX2), respectively, involved in haem metabolism. We analysed whether ALAD rs1800435 alone and their interactions with the four common SNPs in the HMOX1 and HMOX2 genes are associated with the risk for ET.
  
  
  METHODS
  We analysed the genotype and allele variants frequencies of ALAD rs1800435 in 202 patients with familial ET and 218 healthy controls using a TaqMan method. We also analysed the role of the interaction between ALAD rs1800435 and the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363 and HMOX2 rs1051308 with the risk of developing ET.
  
  
  RESULTS
  The frequencies of genotype and allelic variants of ALAD rs1800435 did not differ significantly between patients with ET and controls, and were not influenced by gender. Subjects carrying the ALAD rs1800435CC genotype (wild-type) and the HMOX2 rs1051308GG genotype or the HMOX2 rs1051308G allele had significantly decreased risk for ET.
  
  
  CONCLUSIONS
  These results suggest that the ALAD rs1800435 SNP is not related with the risk for ET, but its interaction with the HMOX2 rs1051308 SNP could be weakly associated with the risk for this disease.
authors.affiliation: Department of Pharmacology, Universidad de Extremadura, Cáceres, Spain.|Research Network on Adverse Reactions to Allergens and Drugs, Madrid, Spain.
authors.forename: José A G
authors.initials: JAG
authors.lastname: Agúndez
authors.affiliation: Department of Pharmacology, Universidad de Extremadura, Cáceres, Spain.|Research Network on Adverse Reactions to Allergens and Drugs, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.affiliation: Department of Medicine-Neurology, Hospital 'Príncipe de Asturias', Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.|Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Alonso-Navarro
authors.affiliation: Department of Pharmacology, Universidad de Extremadura, Cáceres, Spain.|Research Network on Adverse Reactions to Allergens and Drugs, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ayuso
authors.affiliation: Department of Pharmacology, Universidad de Extremadura, Cáceres, Spain.|Research Network on Adverse Reactions to Allergens and Drugs, Madrid, Spain.
authors.forename: Gara
authors.initials: G
authors.lastname: Esguevillas
authors.affiliation: Service of Neurology, Department of Medicine, Hospital Doce de Octubre, Universidad Complutense, Madrid, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Benito-León
authors.affiliation: CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.|Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, Universidad de Navarra, Pamplona, Spain.|Department of Neurology, Clínica Universitaria de Navarra, University of Navarra School of Medicine, Pamplona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ortega-Cubero
authors.affiliation: CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.|Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, Universidad de Navarra, Pamplona, Spain.|Department of Neurology, Clínica Universitaria de Navarra, University of Navarra School of Medicine, Pamplona, Spain.|Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.affiliation: Department of Neurology, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: López-Alburquerque
authors.affiliation: Department of Medicine-Neurology, Hospital 'Príncipe de Asturias', Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.|Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain.
authors.forename: Félix Javier
authors.initials: FJ
authors.lastname: Jiménez-Jiménez
mesh_terms: D000328:Adult; D004843:Epistasis, Genetic; D020329:Essential Tremor / Q000235:genetics*; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000623:Porphobilinogen Synthase / Q000235:genetics*
chemical_list: C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D000623:Porphobilinogen Synthase
keywords: ALAD gene; HMOX1 gene; HMOX2 gene; essential tremor; genetics; lead toxicity