Influence of delta-aminolevulinic acid dehydratase gene polymorphism on selected lead exposure biomarkers in a cohort of ex-smelter workers

J Toxicol Environ Health A. 2013;76(15):895-906. doi: 10.1080/15287394.2013.824843.

Abstract

Lead (Pb) body burden and toxicity may be influenced by genetic polymorphisms. The aim of this study was to investigate the influence of G177C delta-aminolevulinic acid dehydratase (ALAD) polymorphism (rs1800435) on selected Pb exposure biomarkers in a population of workers highly exposed to this metal in the past. A cross-sectional survey was conducted between 2007 and 2009 within the cohort of ex-employees of a smelter in the north of France that closed down in 2003. A questionnaire was completed by each participant and blood samples enabled determination of Pb levels and ALAD polymorphism. Five parameters estimating the Pb body burden and its variations were studied: last blood lead level (BLL) during activity, cumulative blood Pb index, BLL at the time of the study, and absolute and percent changes in BLL after cessation of metal exposure. Multiple regression models were used to evaluate links between ALAD polymorphism and the selected Pb exposure biomarkers. Two hundred and four men were included. At the time of inclusion, the median age was 53.5 yr. The median duration of Pb exposure was 25 yr and the median latency since end of exposure was 5.6 yr. The frequency of ALAD-2 allele was 9.3%, with 34 subjects being heterozygous (ALAD1-2) and 2 homozygous (ALAD2-2). According to genotype, there was no significant difference for any of the five selected Pb exposure biomarkers. These results lend support to the notion that ALAD polymorphism exerts no marked impact on Pb body burden.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Body Burden
  • Cohort Studies
  • Cross-Sectional Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Lead Poisoning / blood
  • Lead Poisoning / enzymology
  • Lead Poisoning / genetics*
  • Male
  • Metallurgy*
  • Middle Aged
  • Occupational Diseases / blood
  • Occupational Diseases / enzymology
  • Occupational Diseases / genetics*
  • Occupational Exposure / adverse effects*
  • Polymorphism, Genetic*
  • Porphobilinogen Synthase / genetics*
  • Porphobilinogen Synthase / metabolism
  • Surveys and Questionnaires
  • Time Factors

Substances

  • Biomarkers
  • Porphobilinogen Synthase