title: Blood lead levels, ALAD gene polymorphisms, and mortality.
abstract: BACKGROUND
  Previous analyses from the National Health and Nutrition Examination Survey (NHANES III) have found that elevated blood lead levels may be associated with cardiovascular mortality, cancer mortality, and all-cause mortality. The 5-aminolevulinic acid dehydratase (ALAD) G177C genetic polymorphism (rs 1800435) affects lead toxicokinetics and may alter the adverse effects of lead exposure. We examined whether the ALAD G177C single nucleotide polymorphism (SNP) affects the relationship between lead and mortality.
  
  
  METHODS
  We analyzed a subset of 3349 genotyped NHANES III participants at least 40 years of age. Using Cox proportional hazards regression, we estimated the relative risk of all-cause, cardiovascular disease, and cancer mortality by ALAD genotype, and by blood lead levels (<5 μg/dL vs. ≥5 μg/dL). We also tested whether the ALAD genotype modified the relationship between blood lead level and mortality.
  
  
  RESULTS
  The adjusted overall relative risk for participants with the variant ALAD genotype was decreased for all-cause mortality (hazards ratio = 0.68; [95% confidence interval = 0.50-0.93]) compared with persons having the common GG genotype. There was some suggestion that higher lead levels were associated with cancer mortality (1.48 [0.92-2.38]). We observed no convincing interaction effect between ALAD genotype and blood lead level on mortality risk.
  
  
  CONCLUSIONS
  The ALAD genotype may be associated with decreased mortality from all causes and from cancer. This association does not seem to be affected by lead exposure.
authors.affiliation: Cancer Prevention Fellowship Program, National Cancer Institute, Rockville, MD 20852, USA. vanbemmeld@mail.nih.gov
authors.forename: Dana M
authors.initials: DM
authors.lastname: van Bemmel
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jody
authors.initials: J
authors.lastname: McLean
authors.forename: Man-Huei
authors.initials: MH
authors.lastname: Chang
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Dowling
authors.forename: Barry
authors.initials: B
authors.lastname: Graubard
authors.forename: Preetha
authors.initials: P
authors.lastname: Rajaraman
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000401:mortality*; D015984:Causality; D005260:Female; D006801:Humans; D007854:Lead / Q000009:adverse effects* / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D009369:Neoplasms / Q000401:mortality*; D009749:Nutrition Surveys; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models
chemical_list: D007854:Lead; D000624:5-Aminolevulinate Synthetase