Genetic Effects on Toxic and Essential Elements in Humans: Arsenic, Cadmium, Copper, Lead, Mercury, Selenium, and Zinc in Erythrocytes

Overview

Journal Environ Health Perspect

Date 2010 Jan 8

PMID 20053595

Citations 30

Authors

John B Whitfield

Veronica Dy

Robert McQuilty

Gu Zhu

Andrew C Heath

Grant W Montgomery

Nicholas G Martin

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: An excess of toxic trace elements or a deficiency of essential ones has been implicated in many common diseases or public health problems, but little is known about causes of variation between people living within similar environments. We estimated effects of personal and socioeconomic characteristics on concentrations of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), selenium (Se), and zinc (Zn) in erythrocytes and tested for genetic effects using data from twin pairs.

Methods: We used blood samples from 2,926 adult twins living in Australia (1,925 women and 1,001 men; 30-92 years of age) and determined element concentrations in erythrocytes by inductively coupled plasma-mass spectrometry. We assessed associations between element concentrations and personal and socioeconomic characteristics, as well as the sources of genetic and environmental variation and covariation in element concentrations. We evaluated the chromosomal locations of genes affecting these characteristics by linkage analysis in 501 dizygotic twin pairs.

Results: Concentrations of Cu, Se, and Zn, and of As and Hg showed substantial correlations, concentrations of As and Hg due mainly to common genetic effects. Genetic linkage analysis showed significant linkage for Pb [chromosome 3, near SLC4A7 (solute carrier family 4, sodium bicarbonate cotransporter, member 7)] and suggestive linkage for Cd (chromosomes 2, 18, 20, and X), Hg (chromosome 5), Se (chromosomes 4 and 8), and Zn {chromosome 2, near SLC11A1 [solute carrier family 11 (proton-coupled divalent metal ion transporters)]}.

Conclusions: Although environmental exposure is a precondition for accumulation of toxic elements, individual characteristics and genetic factors are also important. Identification of the contributory genetic polymorphisms will improve our understanding of trace and toxic element uptake and distribution mechanisms.

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References

Navas-Acien A, Selvin E, Sharrett A, Calderon-Aranda E, Silbergeld E, Guallar E . Lead, cadmium, smoking, and increased risk of peripheral arterial disease. Circulation. 2004; 109(25):3196-201. DOI: 10.1161/01.CIR.0000130848.18636.B2. View

Whitfield J, Fletcher L, MURPHY T, Powell L, Halliday J, Heath A . Smoking, obesity, and hypertension alter the dose-response curve and test sensitivity of carbohydrate-deficient transferrin as a marker of alcohol intake. Clin Chem. 1998; 44(12):2480-9. View

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

Satarug S, Baker J, Urbenjapol S, Haswell-Elkins M, Reilly P, Williams D . A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett. 2002; 137(1-2):65-83. DOI: 10.1016/s0378-4274(02)00381-8. View

Hopper J, Mathews J . Extensions to multivariate normal models for pedigree analysis. II. Modeling the effect of shared environment in the analysis of variation in blood lead levels. Am J Epidemiol. 1983; 117(3):344-55. DOI: 10.1093/oxfordjournals.aje.a113547. View

Wang C, Hsiao C, Chen C, Hsu L, Chiou H, Chen S . A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases. Toxicol Appl Pharmacol. 2007; 222(3):315-26. DOI: 10.1016/j.taap.2006.12.022. View

Virtanen J, Rissanen T, Voutilainen S, Tuomainen T . Mercury as a risk factor for cardiovascular diseases. J Nutr Biochem. 2006; 18(2):75-85. DOI: 10.1016/j.jnutbio.2006.05.001. View

Whitfield J, Dy V, McQuilty R, Zhu G, Montgomery G, Ferreira M . Evidence of genetic effects on blood lead concentration. Environ Health Perspect. 2007; 115(8):1224-30. PMC: 1940084. DOI: 10.1289/ehp.8847. View

Alfven T, Elinder C, Carlsson M, Grubb A, Hellstrom L, Persson B . Low-level cadmium exposure and osteoporosis. J Bone Miner Res. 2000; 15(8):1579-86. DOI: 10.1359/jbmr.2000.15.8.1579. View

10.

Shaper A, Pocock S, Walker M, Wale C, Clayton B, Delves H . Effects of alcohol and smoking on blood lead in middle-aged British men. Br Med J (Clin Res Ed). 1982; 284(6312):299-302. PMC: 1495866. DOI: 10.1136/bmj.284.6312.299. View

11.

Grasmick C, Huel G, Moreau T, Sarmini H . The combined effect of tobacco and alcohol consumption on the level of lead and cadmium in blood. Sci Total Environ. 1985; 41(3):207-17. DOI: 10.1016/0048-9697(85)90142-1. View

12.

Vahter M, Lind B . Concentrations of arsenic in urine of the general population in Sweden. Sci Total Environ. 1986; 54:1-12. DOI: 10.1016/0048-9697(86)90252-4. View

13.

Lloyd B, Lloyd R, Clayton B . Effect of smoking, alcohol, and other factors on the selenium status of a healthy population. J Epidemiol Community Health. 1983; 37(3):213-7. PMC: 1052295. DOI: 10.1136/jech.37.3.213. View

14.

Wasserman G, Liu X, Parvez F, Ahsan H, Factor-Litvak P, Kline J . Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, Bangladesh. Environ Health Perspect. 2007; 115(2):285-9. PMC: 1817715. DOI: 10.1289/ehp.9501. View

15.

Schwartz B, Hu H . Adult lead exposure: time for change. Environ Health Perspect. 2007; 115(3):451-4. PMC: 1849904. DOI: 10.1289/ehp.9782. View

16.

Hasselbalch A, Heitmann B, Kyvik K, Sorensen T . Studies of twins indicate that genetics influence dietary intake. J Nutr. 2008; 138(12):2406-12. DOI: 10.3945/jn.108.087668. View

17.

Borak J, Hosgood H . Seafood arsenic: implications for human risk assessment. Regul Toxicol Pharmacol. 2006; 47(2):204-12. DOI: 10.1016/j.yrtph.2006.09.005. View

18.

Jemal A, Graubard B, Devesa S, Flegal K . The association of blood lead level and cancer mortality among whites in the United States. Environ Health Perspect. 2002; 110(4):325-9. PMC: 1240793. DOI: 10.1289/ehp.02110325. View

19.

Pocock S, Smith M, Baghurst P . Environmental lead and children's intelligence: a systematic review of the epidemiological evidence. BMJ. 1994; 309(6963):1189-97. PMC: 2541690. DOI: 10.1136/bmj.309.6963.1189. View

20.

von Ehrenstein O, Poddar S, Yuan Y, Guha Mazumder D, Eskenazi B, Basu A . Children's intellectual function in relation to arsenic exposure. Epidemiology. 2006; 18(1):44-51. DOI: 10.1097/01.ede.0000248900.65613.a9. View