title: Possible influence of delta-aminolevulinic acid dehydratase polymorphism and susceptibility to renal toxicity of lead: a study of a Vietnamese population.
abstract: We examined six newly identified polymorphisms in the delta-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 alpha1-microglobulin (Ualpha1m), urinary beta2-microglobulin (Ubeta 2m), urinary N-acetyl-beta -d-glucosaminidase (NAG), urinary aminolevulinic acid (ALAU), serum alpha1-microglobulin (Salpha1m), serum beta2-microglobulin (Sbeta 2m), 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 times 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 microg/dL PbB caused an increase of 1.042 mg/g creatinine (Cr) U alpha1m, 1.069 mg/g Cr Ubeta 2m, 1.038 mg/g Cr URBP, and 1.033 mg/g Cr Ualb, whereas in HpyCH4 1-2, an increase of 1 microg/dL PbB resulted in an increase of only 1.009 mg/g Cr Ualpha1m, 1.012 mg/g Cr Ubeta 2m, 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.
authors.affiliation: Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Sin Eng
authors.initials: SE
authors.lastname: Chia
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhou
authors.forename: Mei Theng
authors.initials: MT
authors.lastname: Tham
authors.forename: Eric
authors.initials: E
authors.lastname: Yap
authors.forename: Nguyen-Viet
authors.initials: NV
authors.lastname: Dong
authors.forename: Nguyenthi Hong
authors.initials: NH
authors.lastname: Tu
authors.forename: Kee Seng
authors.initials: KS
authors.lastname: Chia
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D007668:Kidney / Q000187:drug effects*; D007854:Lead / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000235:genetics*; D014744:Vietnam
chemical_list: D007854:Lead; D000623:Porphobilinogen Synthase