Possible Influence of -Aminolevulinic Acid Dehydratase Polymorphism and Susceptibility to Renal Toxicity of Lead: A Study of a Vietnamese Population Sin Eng Chia,1 Huijun Zhou,1 Mei Theng Tham,1 Eric Yap,1 Nguyen-Viet Dong,2 NguyenThi Hong Tu,3 and Kee Seng Chia1 1Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore, Republic of Singapore; 2Center of Occupational Health and Environment, Ministry of Industry, Hanoi, Vietnam; 3General Department of Preventive Medicine and Control of HIV/AIDS Control, Ministry of Health, Hanoi, Vietnam Abstract We examined six newly identified polymorphisms in the -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 1-microglobulin (U1m) , urinary β 2-microglobulin (Uβ 2m) , urinary N-acetyl-β -d-glucosaminidase (NAG) , urinary aminolevulinic acid (ALAU) , serum 1-microglobulin (S1m) , serum β 2-microglobulin (Sβ 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 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) U1m, 1.069 mg/g Cr Uβ 2m, 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 U1m, 1.012 mg/g Cr Uβ 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. Key words: -aminolevulinic acid dehydratase (ALAD) , HpyCH4, intron, lead, SNP (single-nucleotide polymorphism) , urinary albumin (Ualb) , urinary retinol-binding protein (URBP) , urinary 1-microglobulin (U1m) , urinary β 2-microglobulin (Uβ 2m) . Environ Health Perspect 113:1313-1317 (2005) . doi:10.1289/ehp.7904 available via http://dx.doi.org/ [Online 1 June 2005] Address correspondence to S-E. Chia, Department of Community, Occupational and Family Medicine (MD3) , Faculty of Medicine, National University of Singapore, 16 Medical Dr., Singapore 117597, Republic of Singapore. Telephone: 65-68744970. Fax: 65-67791489. E-mail: cofcse@nus.edu.sg We express our appreciation to T.B. Choo, G. Wei, and C.Y. Huak for their generous assistance in the statistical analysis. We thank the management and workers for their participation. This study was supported by research grant from the Agency for Science, Technology and Research, Biomedical Research Council, Singapore (grant 01/1/21/19/186) . The authors declare they have no competing financial interests. Received 3 January 2005 ; accepted 1 June 2005. The full version of this article is available for free in HTML or PDF formats. |