title: Associations of subtypes of hemoglobin with delta-aminolevulinic acid dehydratase genotype and dimercaptosuccinic acid-chelatable lead levels.
abstract: Hemoglobin in erythrocytes may be an important intravascular site of lead binding. We examined associations of hemoglobin subtypes A1 and A2 with delta-aminolevulinic acid dehydratase (ALAD) genotype, a protein that is another important site of erythrocyte lead binding. After oral administration of dimercaptosuccinic acid (DMSA-chelatable lead), we also examined 4-h lead excretion, which provides an estimate of bioavailable lead stores. We randomly selected 57 South Korean current lead battery manufacturing workers from two plants (N = 290 employees) and from two ALAD genotype strata (ALAD1-1 and ALAD1-2). These workers voluntarily administered 5 mg/kg oral DMSA. We frequency-matched subjects with ALAD1-1 (n = 38) to subjects with ALAD1-2 (n = 19) with respect to duration of employment in the lead industry. Blood lead levels ranged from 11 to 53 microg/dl (mean +/- standard deviation, 25.4 +/- 10.2 microg/dl). After administration of oral DMSA, workers excreted a mean lead level of 85.4 (standard deviation, 45.0 microg; range, 16.5-184.1 microg). Hemoglobin A1 and A2 ranged from 3.7% to 9.9% and 1.6% to 5.9%, respectively (mean +/- standard deviation, 6.2 +/- 1.0% and 2.7 +/- 0.8%, respectively). Subjects with ALAD1-1 had elevated mean hemoglobin A1 levels (adjusted p = .05). In addition, higher hemoglobin A1 levels were associated with higher DMSA-chelatable lead levels (adjusted p = .03). This, as well as the results of prior research, suggest that both ALAD and hemoglobin A1 may be important lead-binding sites that influence urinary lead excretion after administration of DMSA.
authors.affiliation: Department of Environmental Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Schwartz
authors.forename: B K
authors.initials: BK
authors.lastname: Lee
authors.forename: W
authors.initials: W
authors.lastname: Stewart
authors.forename: K D
authors.initials: KD
authors.lastname: Ahn
authors.forename: K
authors.initials: K
authors.lastname: Kelsey
authors.forename: J
authors.initials: J
authors.lastname: Bressler
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000483:Alleles; D002614:Chelating Agents / Q000008:administration & dosage*; D005838:Genotype; D006454:Hemoglobins / Q000032:analysis / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007723:Korea; D007854:Lead / Q000009:adverse effects* / Q000032:analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis / Q000706:statistics & numerical data; D000623:Porphobilinogen Synthase / Q000235:genetics*; D011897:Random Allocation; D004113:Succimer / Q000008:administration & dosage*
chemical_list: D002614:Chelating Agents; D006454:Hemoglobins; D007854:Lead; D004113:Succimer; D000623:Porphobilinogen Synthase