Genetic Variation Associated with Hypersensitivity to Mercury

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  • School of Psychology, Deakin University, Victoria ,AU
  • Metabolic Research Unit, School of Medicine, Deakin University, Victoria ,AU
  • Centre for Human Psychopharmacology, Swinburne University of Technology, Victoria ,AU
  • School of Psychology, Deakin University, Victoria ,AU
  • Department of Chemistry and Biotechnology, Swinburne University of Technology, Victoria ,AU
  • School of Psychology, Swinburne University of Technology, Victoria ,AU
  • Metabolic Research Unit, School of Medicine, Deakin University, Victoria ,AU


Genetics, mercury sensitivity, methylenetetrahydrofolate reductase, pink disease, paraoxanase 1


Objectives: Very little is known about mechanisms of idiosyncratic sensitivity to the damaging effects of mercury (Hg); however, there is likely a genetic component. The aim of the present study was to search for genetic variation in genes thought to be involved in Hg metabolism and transport in a group of individuals identified as having elevated Hg sensitivity compared to a normal control group. Materials and Methods: Survivors of pink disease (PD; infantile acrodynia) are a population of clinically identifiable individuals who are Hg sensitive. In the present study, single nucleotide polymorphisms in genes thought to be involved in Hg transport and metabolism were compared across two groups: (i) PD survivors (n = 25); and (ii) age"‘ and sex"‘matched healthy controls (n = 25). Results: Analyses revealed significant differences between groups in genotype frequencies for rs662 in the gene encoding paraoxanase 1 (PON1) and rs1801131 in the gene encoding methylenetetrahydrofolate reductase (MTHFR). Conclusions: We have identified two genetic polymorphisms associated with increased sensitivity to Hg. Genetic variation in MTHFR and PON1 significantly differentiated a group formerly diagnosed with PD (a condition of Hg hypersensitivity) with age"‘ and gender"‘matched healthy controls.


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How to Cite

Austin, D. W., Spolding, B., Gondalia, S., Shandley, K., Palombo, E. A., Knowles, S., & Walder, K. (2018). Genetic Variation Associated with Hypersensitivity to Mercury. Toxicology International, 21(3), 236–241. Retrieved from



Original Research
Received 2018-05-31
Accepted 2018-05-31
Published 2018-06-04



Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. CRC Crit Rev Toxicol 2006;36:609"‘62.

Amin"‘Zaki L, Elhassani S, Majeed MA, Clarkson TW, Doherty RA, Greenwood M. Intra"‘uterine methylmercury poisoning in Iraq. Pediatrics 1974;54:587"‘95.

Tchounwou PB, Ayensu WK, Ninashvili N, Sutton D. Environmental exposure to mercury and its toxicopathologic implications for public health. Environ Toxicol 2003;18:149"‘75.

Zahir F, Rizwi SJ, Haq SK, Khan RH. Low dose mercury toxicity and human health. Environ Toxicol Pharmacol 2005;20:351"‘60.

Ceccatelli S, Daré E, Moors M. Methylmercury"‘induced neurotoxicity and apoptosis. Chem Biol Interact 2010;188:301"‘8.

Swedish Expert Group. Methyl mercury in fish : A toxicologic"‘epidemiologic evaluation of risks: Report from an expert group. Nord Hyg Tidskr Suppl 1971;4:1"‘364.

Berlin M, Zalups RK, Fowler BA. Mercury. In: Nordberg GF, Fowler BA, Nordberg M, Friberg LT, editors. Handbook on the Toxicology of Metals, 3rd Edition. Burlington: Academic Press; 2007. p. 675"‘729.

Summer K"‘H, Halbach S, Kappus H, Greim H. In: Greim H, Snyder R., editors. Toxicology and risk assessment: A comprehensive introduction. 1st edition. West Sussex, United Kingdom: John Wiley and Sons; 2008. 276"‘278.

Verstraeten T, Davis RL, DeStefano F, Lieu TA, Rhodes PH, Black SB, et al. Safety of thimerosal"‘containing vaccines: A two"‘phased study of computerized health maintenance organization databases. Pediatrics 2003;112:1039"‘48.

Mizukoshi K, Nagaba M, Ohno Y, Ishikawa K, Aoyagi M, Watanabe Y, et al. Neurotological studies upon intoxication by organic mercury compounds. ORL J Otorhinolaryngol Relat Spec 1975;37:74"‘87.

Black J. The puzzle of pink disease. J R Soc Med 1999;92:478"‘81.

Dally A. The rise and fall of pink disease. Soc Hist Med 1997;10:291"‘304.

Austin D. An epidemiological analysis of the ‘autism as mercury poisoning' hypothesis. Int J Risk Saf Med 2008;20:135"‘42.

Hock C, Drasch G, Golombowski S, Müller"‘Spahn F, Willershausen"‘Zönnchen B, Schwarz P, et al. Increased blood mercury levels in patients with Alzheimer's disease. J Neural Transm 1998;105:59"‘68.

Haddad LM, Shannon MW, Winchester J. Clinical management of poisoning and drug overdose. 4th edition. Philadelphia: WB Saunders Company; 2007. 1111"‘18

Adams CR, Ziegler DK, Lin JT. Mercury intoxication simulating amyotrophic lateral sclerosis. JAMA 1983;250:642"‘3.

Goetz GG. Textbook of clinical neurology. 3rd ed. St. Louis, MO: Saunders; 2007. 46.

Clarkson TW. The toxicology of mercury. Crit Rev Clin Lab Sci 1997;34:369"‘403.

Barcelos GR, Grotto D, de Marco KC, Valentini J, Lengert Av, Oliveira Aí, et al. Polymorphisms in glutathione"‘related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury. Sci Total Environ 2013;463:319"‘25.

Hernández AF, Gil F, Leno E, López O, Rodrigo L, Pla A. Interaction between human serum esterases and environmental metal compounds. Neurotoxicology 2009;30:628"‘35.

Chen Q, Reis SE, Kammerer CM, McNamara DM, Holubkov R, Sharaf BL, et al. Association between the severity of angiographic coronary artery disease and paraoxonase gene polymorphisms in the National Heart, Lung, And Blood Institute"‘sponsored Women's Ischemia Syndrome Evaluation (WISE) study. Am J Med Genet 2003;72:13"‘22.

Kao YL, Donaghue K, Chan A, Bennetts B, Knight J, Silink M. Paraoxonase gene cluster is a genetic marker for early microvascular complications in type 1 diabetes. Diabet Med 2002;19:212"‘5.

Ou C, Stevenson RE, Brown VK, Schwartz CE, Allen WP, Khoury MJ, et al. 5, 10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects. Am J Med Genet 1996;63:610"‘4.

Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR 677C → T polymorphism and risk of coronary heart disease: A meta"‘analysis. JAMA 2002;288:2023"‘31.

Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM. Folate, vitamin B12, homocysteine, and the MTHFR 677C → T polymorphism in anxiety and depression: The Hordaland Homocysteine Study. Arch Gen Psychiatry 2003;60:618"‘26.

Mills JL, Kirke PN, Molloy AM, Burke H, Conley MR, Lee YJ, et al. Methylenetetrahydrofolate reductase thermolabile variant and oral clefts. Am J Med Genet 1999;86:71"‘4.

Lewis SJ, Lawlor DA, Smith GD, Araya R, Timpson N, Day IN, et al. The thermolabile variant of MTHFR is associated with depression in the British Women's Heart and Health Study and a meta"‘analysis. Mol Psychiatry 2006;11:352"‘60.

Lewis SJ, Zammit S, Gunnell D, Smith GD. A meta"analysis of the MTHFR C677T polymorphism and schizophrenia risk. Am J Med Genet B Neuropsychiatr Genet 2005;135B: 2"‘4.

Muntjewerff JW, Hoogendoorn ML, Kahn RS, Sinke RJ, Heijer MD, Kluijtmans LA, et al. Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: A Dutch population based case"control study. Am J Med Genet B Neuropsychiatr Genet 2005;135B: 69"‘72.

Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M, et al. Geographical and ethnic variation of the 677C > T allele of 5, 10 methylenetetrahydrofolate reductase (MTHFR): Findings from over 7000 newborns from 16 areas world wide. J Med Genet 2003;40:619"‘25.