This study is to determine the distribution of the delta-aminolevulinic acid dehydratase (ALAD) polymorphism among Han subjects of the Chinese population and to study whether the polymorphism in the ALAD gene modifies the toxicity of lead in lead-exposed workers. For this purpose we conducted a cross-sectional study on 156 Chinese workers who were exposed to lead in lead-acid battery and electric-flex manufacturing plants. The authors found that the allele frequencies of ALAD1 and ALAD2 were 0.9679 and 0.0321, respectively. Workers with the ALAD 1-1 genotype were associated with higher blood lead levels than those with the ALAD 1-2 genotype. Blood and urine lead levels were much higher in storage battery workers than in cable workers. The self-conscious symptom survey showed that the incidences of debilitation, amnesia and dreaminess were much higher in those had more than five years of tenure or contact with lead on the job within the ALAD 1-1 genotype subgroup. Laboratory examinations showed that serum iron and zinc levels in workers’ with the ALAD 1-2 genotype were higher than those with the ALAD 1-1 genotype, especially in storage-battery workers. Correlation analysis indicated that the blood lead level negatively correlated with serum calcium, iron and zinc level. The data of this study suggest that the ALAD gene polymorphism and serum ion levels may modify the kinetics of lead in blood. Therefore, the authors recommend that an adequate intake of dietary calcium, iron, and zinc or the calcium, iron, and zinc supplementation should be prescribed to Chinese lead exposed workers.
References
[1]
Yedjou, C.G.; Milner, J.N.; Howard, C.B.; Tchounwou, P.B. Basic apoptotic mechanisms of lead toxicity in human leukemia (HL-60) cells. Int. J. Environ. Res. Public Health 2010, 7, 2008–2017, doi:10.3390/ijerph7052008. 20623007
[2]
Kelada, S.N.; Shelton, E.; Kaufmann, R.B.; Khoury, M.J. Delta-aminolevulinic acid dehydratase genotype and lead toxicity: A HuGE review. Am. J. Epidemiol. 2001, 154, 1–13, doi:10.1093/aje/154.1.1. 11427399
[3]
Jaffe, E.K. The porphobilinogen synthase family of metalloenzymes. Acta Crystallogr. Biol. Crystallogr. 2000, 56, 115–128, doi:10.1107/S0907444999014894.
[4]
Battistuzzi, G.; Petrucci, R.; Silvagni, L.; Urbani, F.R.; Caiola, S. δ-Aminolevulinate dehydrase: A new genetic polymorphism in man. Ann. Hum. Genet. 1981, 45, 223–229, doi:10.1111/j.1469-1809.1981.tb00333.x.
[5]
Onalaja, A.O.; Claudio, L. Genetic susceptibility to lead poisoning. Environ. Health Perspect. 2000, 108(Suppl 1), 23–28. 11333195
[6]
Patil, A.J.; Bhagwat, V.R.; Patil, J.A.; Dongre., N.N.; Ambekar, J.G.; Jailkhani, R.; Das, K.K. Effect of lead (Pb) exposure on the activity of superoxide dismutase and catalase in battery manufacturing workers (BMW) of Western Maharashtra (India) with reference to heme biosynthesis. Int. J. Environ. Res. Public Health 2006, 3, 329–337, doi:10.3390/ijerph2006030041.
[7]
Lin-Fu, J.S. Vulnerability of children to lead exposure and toxicity: Part one. N. Engl. J. Med. 1973, 289, 1229–1233, doi:10.1056/NEJM197312062892306.
[8]
Ziegler, E.E.; Edwards, B.B.; Jensen, R.L.; Mahaffey, K.R.; Fomon, S.J. Absorption and retention of lead by infants. Pediatr. Res. 1978, 12, 29–34, doi:10.1203/00006450-197801000-00008. 643372
[9]
Wetmur, J.G.; Kaya, A.H.; Plewinska, M.; Desnick, R.J. Molecular characterization of the human δ-aminolevulinate dehydratase 2 (ALAD2) allele: Implications for molecular screening of individuals for genetic susceptibility to lead poisoning. Am. J. Hum. Genet. 1991, 49, 757–763. 1716854
[10]
Smith, C.M.; Wang, X.; Hu, H.; Kelsey, K.T. A polymorphism in the δ-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead. Environ. Health Perspect. 1995, 103, 248–253. 7768225
[11]
Benkmann, H.G.; Bogdanski, P.; Goedde, H.W. Polymorphism of δ-aminolevulinic acid dehydratase in various populations. Hum. Hered. 1983, 33, 62–64, doi:10.1159/000153351.
[12]
Hsieh, L.L.; Liou, S.H.; Chen, Y.H.; Tsai, L.C.; Yang, T.; Wu, T.N. Association between aminolevulinate dehydrogenase genotype and blood lead levels in Taiwan. J. Occup. Environ. Med. 2000, 42, 151–155, doi:10.1097/00043764-200002000-00009.
[13]
Miyaki, K.; Lwin, H.; Masaki, K.; Song, Y.; Takahashi, Y.; Muramatsu, M.; Nakayama, T. Association between a polymorphism of aminolevulinate dehydrogenase (ALAD) gene and blood lead levels in Japanese subjects. Int. J. Environ. Res. Public Health 2009, 6, 999–1009, doi:10.3390/ijerph6030999. 19440429
[14]
Ziemsen, B.; Angerer, J.; Lehnert, G.; Benkmann, H.G.; Goedde, H.W. Polymorphism of δ-aminolevulinic acid dehydratase in lead-exposed workers. Int. Arch. Occup. Environ. Health 1986, 58, 245–247, doi:10.1007/BF00432107.
[15]
Wetmur, J.G.; Lehnert, G.; Desnick, R.J. The δ-aminolevulinate dehydratase polymorphism: Higher blood lead levels in lead workers and environmentally exposed children with the 1-2 and 2-2 isozymes. Environ. Res. 1991, 56, 109–119, doi:10.1016/S0013-9351(05)80001-5.
[16]
Schwartz, B.S.; Lee, B.K.; Stewart, W.; Ahn, K.D.; Springer, K.; Kelsey, K. Associations of δ-aminolevulinic acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers. Am. J. Epidemiol. 1995, 142, 738–745. 7572945
[17]
Shaik, A.P.; Jamil, K. A study on the ALAD gene polymorphisms associated with lead exposure. Toxicol. Ind. Health 2008, 24, 501–506, doi:10.1177/0748233708095770.
[18]
Bellinger, D.C. The protean toxicities of lead: New chapters in a familiar story. Int. J. Environ. Res. Public Health 2011, 8, 2593–2628, doi:10.3390/ijerph8072593.
[19]
Kiran, K.B.; Prabhakara, R.Y; Noble, T.; Weddington, K.; McDowell, V.P.; Rajanna, S.; Bettaiya, R. Lead-induced alteration of apoptotic proteins in different regions of adult rat brain. Toxicol. Lett. 2009, 184, 56–60, doi:10.1016/j.toxlet.2008.10.023.
[20]
NourEddine, D.; Miloud, S.; Abdelkader, A. Effect of lead exposure on dopaminergic transmission in the rat brain. Toxicology 2005, 207, 363–368, doi:10.1016/j.tox.2004.10.016.
[21]
Jiang, Y.M.; Long, L.L.; Zhu, X.Y.; Zheng, H.; Fu, X.; Ou, S.Y.; Wei, D.L.; Zhou, H.L.; Zheng, W. Evidence for altered hippocampal volume and brain metabolites in workers occupationally exposed to lead: A study by magnetic resonance imaging and 1H magnetic resonance spectroscopy. Toxicol. Lett. 2008, 181, 118–125, doi:10.1016/j.toxlet.2008.07.009.
[22]
Krieg, E.F.; Butler, M.A.; Chang, M.H.; Liu, T.; Yesupriya, A.; Lindegren, M.L.; Dowling, N. Lead and cognitive function in ALAD genotypes in the third National Health and Nutrition Examination Survey. Neurotoxicol. Teratol. 2009, 31, 364–371, doi:10.1016/j.ntt.2009.08.003.
[23]
Rajan, P.; Kelsey, K.T.; Schwartz, J.D.; Bellinger, D.C.; Weuve, J.; Sparrow, D.; Spiro, A.; Smith, T.J.; Nie, H.; Hu, H.; Wright, R.O. Lead burden and psychiatric symptoms and the modifying influence of the delta-aminolevulinic acid dehydratase (ALAD) polymorphism: The VA Normative Aging Study. Am. J. Epidemiol. 2007, 166, 1400–1408, doi:10.1093/aje/kwm220.
[24]
Weuve, J.; Kelsey, K.T.; Schwartz, J.; Bellinger, D.; Wright, R.O.; Rajan, P.; Spiro, A.; Sparrow, D.; Aro, A.; Hu, H. Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: The Normative Aging Study. Occup. Environ. Med. 2006, 63, 746–753, doi:10.1136/oem.2006.027417.
[25]
Pizent, A.; Jurasovic, J.; Telisman, S. Serum calcium, zinc, and copper in relation to biomarkers of lead and cadmium in men. J. Trace Elem. Med. Biol. 2003, 17, 199–205, doi:10.1016/S0946-672X(03)80026-3.
[26]
Bradberry, S.; Vale, A. A comparison of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. Clin. Toxical.(Phila.) 2009, 47, 841–858, doi:10.3109/15563650903321064.
[27]
Pires, J.B.; Miekeley, N.; Donangelo, C.M. Calcium supplementation during lactation blunts erythrocyte lead levels and delta-aminolevulinic acid dehydratase zinc-reactivation in women non-exposed to lead and with marginal calcium intakes. Toxicology 2002, 175, 247–255, doi:10.1016/S0300-483X(02)00091-4.
[28]
Ettinger, A.S.; Lamadrid, F.H.; Tellez, R.M.M.; Mercado, G.A.; Peterson, K.E.; Schwartz, J.; Hu, H.; Hernandez, A.M. Effect of calcium supplementation on blood lead levels in pregnancy: A randomized placebo-controlled trial. Environ. Health Perspect. 2009, 117, 26–31. 19165383
[29]
Varnai, V.M.; Piasek, M.; Blanusa, M.; Saric, M.M.; Simic, D.; Kostial, K. Calcium supplementation efficiently reduces lead absorption in suckling rats. Pharmacol. Toxicol. 2001, 89, 326–330, doi:10.1034/j.1600-0773.2001.d01-169.x. 11903960
[30]
Markowitz, M.E.; Sinnett, M.; Rosen, J.F. A randomized trial of calcium supplementation for childhood lead poisoning. Pediatrics 2004, 113, 34–39, doi:10.1542/peds.113.1.e34.
[31]
Konofal, E.; Cortese, S. Lead and neuroprotection by iron in ADHD. Environ. Health Perspect. 2007, 115, 398–399, doi:10.1289/ehp.10304.
[32]
Muwakkit, S.; Nuwayhid, I.; Nabulsi, M.; Hajj, R.; Khoury, R.; Mikati, M.; Abboud, M.R. Iron deficiency in young Lebanese children: Association with elevated blood lead levels. J. Pediatr. Hematol. Oncol. 2008, 30, 382–386, doi:10.1097/MPH.0b013e318165b283.
[33]
Wang, Q.; Luo, W.; Zheng, W.; Liu, Y.; Xu, H.; Zheng, G.; Dai, Z.; Zhang, W.; Chen, Y.; Chen, J. Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development. Toxicol. Appl. Pharmacol. 2007, 219, 33–41, doi:10.1016/j.taap.2006.11.035.
[34]
Kim, H.S.; Lee, S.S.; Hwangbo, Y.; Ahn, K.D.; Lee, B.K. Cross-sectional study of blood lead effects on iron status in Korean lead workers. Nutrition 2003, 19, 571–576, doi:10.1016/S0899-9007(03)00035-2. 12831940
[35]
Kordas, K.; Stoltzfus, R.J.; Lopez, P.; Rico, J.A.; Rosado, J.L. Iron and zinc supplementation does not improve parent or teacher ratings of behavior in first grade Mexican children exposed to lead. J. Pediatr. 2005, 147, 632–639, doi:10.1016/j.jpeds.2005.06.037.
[36]
Serwint, J.R.; Damokosh, A.I.; Berger, O.G.; Chisolm, J.J.; Gunter, E.W.; Jones, R.L.; Rhoads, G.G.; Rogan, W. No difference in iron status between children with low and moderate lead exposure. J. Pediatr. 1999, 135, 108–110, doi:10.1016/S0022-3476(99)70338-0.
[37]
Winneke, G. Zinc to prevent lead poisoning. Can. Med. Assoc. J. 1996, 154, 1622–1623.
[38]
Batra, N.; Nehru, B.; Bansal, M.P. The effect of zinc supplementation on the effects of lead on the rat testis. Reprod. Toxicology 1998, 12, 535–540, doi:10.1016/S0890-6238(98)00030-6.
[39]
Rico, J.A.; Kordas, K.; Lopez, P.; Rosado, J.L.; Vargas, G.G.; Ronquillo, D.; Stoltzfus, R.J. Efficacy of iron and/or zinc supplementation on cognitive performance of lead-exposed Mexican schoolchildren: A randomized, placebo-controlled trial. Pediatrics 2006, 117, 518–527, doi:10.1542/peds.2005-1172.
[40]
De Castro, C.S.; Arruda, A.F.; Da Cunha, L.R.; De Souza, J.R.; Braga, J.W.; Dórea, J.G. Toxic metals (Pb and Cd) and their respective antagonists (Ca and Zn) in infant formulas and milk marketed in Brasilia, Brazil. Int. J. Environ. Res. Public Health 2010, 7, 4062–4077, doi:10.3390/ijerph7114062. 21139877
