Top

International Archives of Occupational and Environmental Health

Published in:

01-08-2012 | Original Article

The effects of metallothionein 2A polymorphism on lead metabolism: are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels?

Authors: Deniz Tekin, Zeliha Kayaaltı, Tülin Söylemezoğlu

Published in: International Archives of Occupational and Environmental Health | Issue 6/2012

Abstract

Objectives

Numerous studies indicate that certain genetic polymorphisms modify lead toxicokinetics. Metallothioneins are protective against the toxicity of many metals, including lead. The aim of this study was to determine whether the maternal metallothionein 2A (MT2A) -5 A/G single-nucleotide polymorphism is related to the lead levels in maternal blood, placental tissue and cord blood in 91 pregnant women and their newborns.

Methods

Venous blood from the mother was collected to investigate lead levels and MT2A polymorphism. Cord blood and placenta were collected for lead levels. Analyses were made using an Atomic Absorption Graphite Furnace Spectrophotometer. Standard PCR–RFLP technique was used to determine MT2A polymorphism.

Results

Blood lead levels of heterozygote genotype (AG) mothers were statistically higher than those of homozygote genotype (AA) (P < 0.05). Maternal lead levels were significantly associated with cord blood lead levels for pregnant women with AA genotype (P < 0.001). This association was not statistically significant for pregnant women with AG. In contrast, the mean value of cord blood lead level for newborns with mothers of AG genotype was slightly higher than others, though the difference was not significant. No significant difference existed in placenta lead levels between the groups.

Conclusion

This study suggests that pregnant women with AG genotype for MT2A polymorphism might have high blood lead levels and their newborns may be at risk of low-level cord blood lead variation.

Baghurst PA, Robertson EF, Oldfield RK, King BM, McMichael AJ, Vimpani GV, Wigg NR (1991) Lead in the placenta, membranes, and umbilical cord in relation to pregnancy outcome in lead smelter community. Environ Health Perspect 90:315–320CrossRef

Black AJ, Topping J, Durham B, Farquharson RG, Fraser WD (2000) A detailed assessment of alternations in bone turnover, calcium homeostasis, and bone density in normal pregnancy. J Bone Miner Res 15:557–563CrossRef

Braun JM, Froehlich TE, Daniels JL, Dietrich KN, Hornung R, Auinger P, Lanphear BP (2008) Association of environmental toxicants and conduct disorder in US children: NHANES 2001–2004. Environ Health Perspect 116:956–962CrossRef

Canfield RL, Henderson CR, Cory-Slectha DA, Cox C, Jusko TA, Lanphear BP (2003) Intellectual impairment in children with blood lead concentrations below 10 microg/dl. N Engl J Med 348:1517–1526CrossRef

Carrillo-Ponce ML, Martinez-Ordaz VA, Velasco-Rodriquez VM, Hernandez-Garcia A, Hernandez-Serrano MC, Sanmiquel F (2004) Serum lead, cadmium and zinc levels in newborns with neural tube defects from a polluted zone in Mexico. Reprod Toxicol 19:149–154CrossRef

Dorea JG (2004) Mercury and lead during breast-feeding. Br J Nutr 92:21–40CrossRef

Durska G, Kozielec T, Karakiewicz B (2002) Evaluation of transplacental gradient for cadmium and lead. Ginekol Pol 73:43–49

Furman A, Lalefi M (2001) Maternal and umbilical cord blood lead levels. Arch Environ Health 56:26–28CrossRef

Gardella C (2001) Lead exposure in pregnancy: a review of the literature and argument for routine prenatal screening. Obstet Gynecol Surv 56:231–238CrossRef

Garvey JS (1984) Metallothionein: structure/antigenicity and detection/quantitation in normal physiological fluids. Environ Health Perspect 54:117–127CrossRef

Goering PL (1993) Lead-protein interactions as a basis for lead toxicity. Neurotoxicology 14:45–60

Goyer RA (1990) Transplacental transport of lead. Environ Health Perspect 89:101–105

Goyer RA (1997) Toxic and essential metal interactions. Annu Rev Nutr 17:37–50CrossRef

Gundacker C, Wittmann KJ, Kukuckova M, Komarnicki G, Hikkel I, Gencik M (2009) Genetic background of lead and mercury metabolism in a group of medical students in Austria. Environ Res 109:786–796CrossRef

Hwang YH, Wang JD (1990) Temporal fluctuation of the lead level in the cord blood of neonates in Taipei. Arch Environ Health 45:42–45CrossRef

Hwang YH, Ko Y, Chiang CD, Hsu SP, Lee YH, Yu CH, Chiou CH, Wang JD, Chuang HY (2004) Transition of cord blood lead level, 1985–2002, in the Taipei area and its determinants after the cease of leaded gasoline use. Environ Res 96:274–282CrossRef

Ikebuchi H, Teshima R, Suzuki K, Terao T, Yamane Y (1986) Stimultaneous induction of Pb- metallothionein-like protein and Zn- thionein in the liver of rats given lead acetate. Biochem J 233:541–546

Jedrychowski W, Perera F, Jankowski J, Mrozek-Budzyn D, Mroz E, Flak E, Edwards S, Skarupa A, Lisowska-Miszczy I (2009) Gender specific differences in neurodevelopmental effects of prenatal exposure to very low-lead levels: the prospective cohort study in three- year olds. Early Hum Dev 85:503–510CrossRef

Jusko TA, Henderson Jr, Lanphear BP, Cory-Slechta DA, Parsons RL (2008) Blood lead concentrations <10 μg/dl and child intelligence at 6 years of age. Environ Health Perspect 116:243–248CrossRef

Kägi JH (1991) Overview of metallothionein. Methods Enzymol 205:613–626CrossRef

Kayaalti Z, Söylemezoğlu T (2010) The polymorphism of core promoter region on metallothionein 2A- metal binding protein in Turkish population. Mol Biol Rep 37:185–190CrossRef

Kayaalti Z, Mergen G, Söylemezoğlu T (2010) Effect of metallothionein core promoter region polymorphism on cadmium, zinc and copper levels in autopsy kidney tissues from a Turkish population. Toxicol Appl Pharmacol 245:252–255CrossRef

Kayaaltı Z, Aliyev V, Söylemezoğlu T (2011) The potential effect of metallothionein 2A–5 A/G single nucleotide polymorphism on blood cadmium, lead, zinc and copper levels. Toxicol Appl Pharmacol 256:1–7CrossRef

Khan AH, Khan A, Ghani F, Khurshid M (2001) Low-level lead exposure and blood lead levels in children: a cross-sectional survey. Arch Environ Health 56:501–505CrossRef

Kita K, Miura N, Yoshida N, Yamazaki M, Ohkubo K, Imai T, Naganuma YA (2006) Potential effect on cellular response to cadmium of a single- nucleotide A –>G polymorphism in the promoter of the human gene for metallothionein IIA. Hum Genet 120:553–560CrossRef

Lafond J, Hamel A, Tasker L, Vaillancourt C, Mergler D (2004) Low environmental contamination by lead in pregnant women: effect on calcium transfer in human placental syncytiotrophoblasts. J Toxicol Environ Health A 67:1069–1079CrossRef

Lanphear BP, Dietrich K, Auinger P, Cox C (2000) Cognitive deficits associated with blood lead concentrations <10 microg/dl in US children and adolescents. Public Health Rep 115:512–529CrossRef

Lewendon G, Kinra S, Nelder R, Cronin T (2001) Should children with developmental and behavioural problems be routinely screened for lead? Arch Dis Child 85:286–288CrossRef

Liu J, Cheng ML, Yang Q, Shan KR, Shen J, Zhou Y, Zhang X, Dill AL, Waalkes MP (2007) Blood metallothionein transcript as a biomarker for metal sensitivity: low blood metallothionein transcripts in arsenicosis patients from Guizhou, China. Environ Health Perspect 115:1101–1106CrossRef

Mazur LJ (2003) Paediatric environmental health. Curr Prob Ped Adolesc Health Care 33:6–25CrossRef

Miranda ML, Kim D, Galeano MA, Paul CJ, Hull AP, Morgan SP (2007) The relationship between early childhood blood lead levels and performance on end-of-grade tests. Environ Health Perspect 115:1242–1247CrossRef

Nordberg M (1998) Metallothioneins: historical review and state of knowledge. Talanta 46:243–254CrossRef

Osman K, Akesson A, Berglund M, Bremme K, Schütz A, Ask K, Vahter M (2000) Toxic and essential elements in placentas of Swedish women. Clin Biochem 33:131–138CrossRef

Qu W, Diwan BA, Liu J, Goyer RA, Dawson T, Horton JL, Cherian MG, Waalkes MP (2002) The metallothionein-null phenotype is associated with heightened sensitivity to lead toxicity and an inability to form inclusion bodies. Am J Pathol 160:1047–1056CrossRef

Rogan WJ, Ware JH (2003) Exposure to lead in children: how low is low enough? N Engl J Med 348:1515–1516CrossRef

Ronchetti R, Hazel-Van Den P, Schoeters G, Hanke W, Rennezova Z, Barreto M, Villa-Pia M (2006) Lead neurotoxicity in children: is prenatal exposure more important than postnatal exposure? Acta Paediatr Suppl 95:45–49CrossRef

Skroch P, Buchman C, Karin M (1993) Regulation of human and yeast metallothionein gene transcription by heavy metal ions. Prog Clin Biol Res 380:113–128

Soong YK, Tseng R, Liu C, Lin PW (1991) Lead, cadmium, arsenic, and mercury levels in maternal and fetal cord blood. J Formos Med Assoc 90:59–65

Tekin D, Kayaaltı Z, Aliyev V, Söylemezoğlu T (2011) The effects of metallothionein 2A polymorphism on placental cadmium accumulation: is metallothionein a modifying factor in transfer of micronutrients to the fetus? J Appl Toxicol. doi:10.1002/jat.1661 (In press)

Tong S (1998) Lead exposure and cognitive development: persistence and a dynamic pattern. J Paediatr Child Health 34:114–118CrossRef

Truska P, Rosival L, Balázová G, Hinst J, Rippel A, Palusová O, Grunt J (1989) Blood and placental concentrations of cadmium, lead, and mercury in mothers and their newborns. J Hyg Epidemiol Microbio Immunol 33:141–147

Waalkes MP, Harvey MJ, Klaassen CD (1984) Relative in vitro affinity of hepatic metallothionein for metals. Toxicol Lett 20:33–39CrossRef

Waalkes MP, Liu J, Goyer RA, Diwan BA (2004) Metallothionein-I/II double knockout mice are hypersensitive to lead-induced kidney carcinogenesis: role of inclusion body formation. Cancer Res 64:7766–7772CrossRef

Yamaga A, Taga M, Minaguchi H (2000) Changes in urinary excretions of C- telopepdide of type I collagen during pregnancy and lactation. Ann Rev Nutr 20:249–272CrossRef

Title: The effects of metallothionein 2A polymorphism on lead metabolism: are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels?
Authors: Deniz Tekin
Zeliha Kayaaltı
Tülin Söylemezoğlu
Publication date: 01-08-2012
Publisher: Springer-Verlag
Published in: International Archives of Occupational and Environmental Health / Issue 6/2012
Print ISSN: 0340-0131
Electronic ISSN: 1432-1246
DOI: https://doi.org/10.1007/s00420-011-0711-y

At a glance: The STEP trials

Springer Medicine

The effects of metallothionein 2A polymorphism on lead metabolism: are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels?

Abstract

Objectives

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2012

Neuromotor function in ship welders after cessation of manganese exposure

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model

The relative contribution of work exposure, leisure time exposure, and individual characteristics in the onset of arm–wrist–hand and neck–shoulder symptoms among office workers

Working conditions of female part-time and full-time teachers in relation to health status

Acute effects of mechanical shocks on finger blood flow: influence of shock repetition rate and shock magnitude

Longitudinal evidence for the association between work-related physical exposures and neck and/or shoulder complaints: a systematic review