title: Lead concentration in plasma as a biomarker of exposure and risk, and modification of toxicity by δ-aminolevulinic acid dehydratase gene polymorphism.
abstract: Blood lead concentration (B-Pb), the main biomarker of lead exposure and risk, is curvi-linearily related to exposure. We assessed plasma lead (P-Pb) as a marker for both lead exposure and toxic effects. We examined claims that δ-aminolevulinic acid dehydratase genotype (ALAD) can modify lead toxicity. In 290 lead-exposed and 91 unexposed Chinese workers, we determined P-Pb, B-Pb, urinary lead (U-Pb), ALAD polymorphism (rs1800435, ALAD1/2; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary δ-aminolevulic acid), on the kidneys (urinary albumin, β2-microglobulin and N-acetyl-β-d-glucosaminidase) and on the peripheral nervous system (sensory and motor conduction velocities). In exposed workers, median P-Pb was 4.10 (range 0.35-27)μg/L, B-Pb 401 (110-950)μg/L, and U-Pb 188 (22-590)μg/g creatinine. P-Pb had a higher ratio between exposed and unexposed workers (median 39, range 18-110) than B-Pb (19, 15-36; p<0.001) and U-Pb (28, 15-36; p<0.001). All three biomarkers were associated with all toxic effects (P-Pb: rS=-0.10 to 0.79; B-Pb: rS=-0.08 to 0.75; all p<0.05). In the exposed workers, B-Pb and U-Pb were significantly higher (p=0.04) in ALAD2 carriers (7% in the exposed population) than in ALAD1 homozygotes. P-Pb values were similar; ALAD1 homozygotes suffered higher kidney toxicity at the same P-Pb.
  
  
  CONCLUSIONS
  (i) P-Pb has advantages over B-Pb as a biomarker of high Pb exposure, but it was not significantly better as an index of risk of toxicity. (ii) The ALAD genotype modifies toxicokinetics and toxicodynamics.
authors.affiliation: Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 200032 Shanghai, PR China.
authors.forename: Liting
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 200032 Shanghai, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Johan Nilsson
authors.initials: JN
authors.lastname: Sommar
authors.affiliation: Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 200032 Shanghai, PR China; Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, SE-90187 Umeå, Sweden. Electronic address: yihuai.liang@fudan.edu.cn.
authors.forename: Yihuai
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Division of Occupational and Environmental Medicine, University Hospital, SE-22185 Lund, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Lundh
authors.affiliation: Division of Occupational and Environmental Medicine, University Hospital, SE-22185 Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Broberg
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, 030001 Taiyuan, PR China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Lei
authors.affiliation: Shengzhou Municipal Center for Disease Control and Prevention, 312400 Zhejiang Province, PR China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Guo
authors.affiliation: Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 201800 Shanghai, PR China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 201800 Shanghai, PR China.
authors.forename: Mingguang
authors.initials: M
authors.lastname: Tan
authors.affiliation: Division of Occupational and Environmental Medicine, University Hospital, SE-22185 Lund, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Skerfving
authors.affiliation: Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 200032 Shanghai, PR China. Electronic address: tyjin@shmu.edu.cn.
authors.forename: Taiyi
authors.initials: T
authors.lastname: Jin
authors.affiliation: Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Ingvar A
authors.initials: IA
authors.lastname: Bergdahl
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D044466:Asian People; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002681:China; D005260:Female; D059647:Gene-Environment Interaction; D006454:Hemoglobins / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000097:blood* / Q000633:toxicity* / Q000652:urine; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D017933:Peripheral Nervous System / Q000187:drug effects / Q000378:metabolism; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000235:genetics*; D011524:Protoporphyrins / Q000097:blood; D011795:Surveys and Questionnaires; D066007:Toxicokinetics; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D011524:Protoporphyrins; D001613:beta 2-Microglobulin; C017803:zinc protoporphyrin; D007854:Lead; D000118:Acetylglucosaminidase; D000623:Porphobilinogen Synthase
keywords: Gene–environment interaction; Lead; Occupational exposure; Plasma; δ-Aminolevulinic acid dehydratase gene