Possible Influence of δ-Aminolevulinic Acid Dehydratase Polymorphism and Susceptibility to Renal Toxicity of Lead: A Study of a Vietnamese Population
National Institute of Environmental Health Sciences -- Environmental Health Perspectives
DOI 10.1289/ehp.7904
  1. δ-aminolevulinic acid dehydratase (ALAD)
  2. HpyCH4
  3. intron
  4. lead
  5. SNP (single-nucleotide polymorphism)
  6. urinary albumin (Ualb)
  7. urinary retinol-binding protein (URBP)
  8. urinary α1-microglobulin (Uα1m)
  9. urinary β2-microglobulin (Uβ2m)

We examined six newly identified polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) single-nucleotide polymorphisms (SNPs) to determine if these SNPs could modify the relationship between blood lead (PbB) and some renal parameters. This is a cross-sectional study of 276 lead-exposed workers in Vietnam. All workers were measured for PbB, urinary retinol-binding protein (URBP), urinary α1-microglobulin (Uα1m), urinary β2-microglobulin (Uβ2m), urinary N-acetyl-β-d-glucosaminidase (NAG), urinary aminolevulinic acid (ALAU), serum α1-microglobulin (Sα1m), serum β2-microglobulin (Sβ2m), and urinary albumin (Ualb). The six SNPs were Msp and Rsa in exon 4, Rsa39488 in exon 5, HpyIV and HpyCH4 in intron 6, and Sau3A in intron 12. Analysis of covariance (ANCOVA) with interaction of PbB × SNPs were applied to examine modifying effect of the SNPs on the association of renal parameters and PbB, adjusting for potential confounders of age, gender, body mass index, and exposure duration. HpyCH4 was found to be associated with certain renal parameters. For HpyCH4 1-1, an increase of 1 μg/dL PbB caused an increase of 1.042 mg/g creatinine (Cr) Uα1m, 1.069 mg/g Cr Uβ2m, 1.038 mg/g Cr URBP, and 1.033 mg/g Cr Ualb, whereas in HpyCH4 1-2, an increase of 1 μg/dL PbB resulted in an increase of only 1.009 mg/g Cr Uα1m, 1.012 mg/g Cr Uβ2m, 1.009 mg/g Cr URBP, and 1.007 mg/g Cr Ualb. HpyCH4 SNP appeared to modify the lead toxicity to kidney with wild-type allele being more susceptible than variants. The mechanism for this effect is not clear. Further studies are needed to confirm this observation.