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Methyl mercury metabolism in man influenced by genetic factors


Exposure to toxic methylmercury (MeHg) mainly through fish consumption is a large problem worldwide, and it has led to governmental recommendations for reducing fish consumption and blacklisting of highly contaminated fish (see EVISA's news section below). Risk assessment for different populations is complicated by the fact that elimination kinetics of MeHg varies greatly among individuals. The elimination half-time of MeHg varies greatly among individuals, ranging from 45 to 70 days (Clarkson 2002), but extreme values, up to almost 190 days, have been reported (Al-Shahristani and Shihab 1974).  One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate.

The new study:
The Swedish research group conducted this study to assess the influence of polymorphisms in GSH-synthesizing genes on MeHg retention. They measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake) from 292 subjects from northern Sweden that had a high consumption of fish (lean/fat fish two to three times per week or more).

Results of the present study indicate that polymorphisms in GCLM and GST genes modify the relationship between exposure to and retention of MeHg. Two polymorphisms in GSTP1 modified the Ery-Hg levels at high MeHg exposures, whereas homozygotes for the GCLM-588 polymorphism had higher Ery-Hg levels but showed no evidence of effect modification.

Another outcome of the study was the rise of Ery-Hg with increasing age. Increasing age may also be associated with impairment of the metabolism of MeHg. Indeed, both GSH and GST levels have been shown to decrease with age (Voss and Siems 2006).

The researchers concluded their report by stressing the importance of information on genetic impact on MeHg metabolism, because it may mean a difference in susceptibility to toxic effects, which may influence the risk assessment and thus the foundation of preventive actions.

The new study:

Karin Schläwicke Engström, Ulf Strömberg, Thomas Lundh, Ingegerd Johansson, Bengt Vessby, Göran Hallmans, Staffan Skerfving, Karin Broberg, Genetic Variation in Glutathione-Related Genes and Body Burden of Methylmercury, Environ. Health Perspect., 116/6 (2008) 734-739. doi:10.1289/ehp.10804

Related studies:

H. Al-Shahristani, K.M. Shihab, Variation of biological half-life of methylmercury in man, Arch. Environ. Health, 28 (1974) 342-344.
N. Ballatori, T.W. Clarkson,  Biliary secretion of glutathione and of glutathione-metal complexes, Fundam. Appl. Toxicol., 5  (1985) 816-831. doi:10.1016/0272-0590(85)90165-4
W.J. Dutczak, N. Ballatori, Transport of the glutathione-methylmercury complex across liver canalicular membranes on reduced glutathione carriers, J. Biol. Chem., 269 (1994) 9746-9751.
T.W. Clarkson, The three modern faces of mercury, Environ. Health Perspect., 110/S.1 (2002) 11-23.
H.M. Custodio, K. Broberg, M. Wennberg, J.H. Jansson, B. Vessby, G. Hallmans, Polymorphisms in glutathione-related genes affect methylmercury retention, Arch. Environ. Health, 59 (2004) 588-595.

Related News

EVISA News, March 11, 2007: Methylmercury contamination of fish warrants worldwide public warning
EVISA News, May 3, 2006: Texas Study Relates Autism to Environmental Mercury
EVISA News, February 9, 2006, Study show high levels of mercury in women related to fish consumption
EVISA News, August 29, 2005: Is methyl mercury limiting the delight of seafood ? - To answer this question is a challenge for elemental speciation analysis
EVISA News, June 27, 2005: Susceptibility to arsenic toxicity influenced by genes
EVISA News, January 12, 2005: Number of fish meals is a good predictor for the mercury found in hair of environmental journalists
EVISA News, April 27, 2004: New kind of mercury found in fish
EVISA News, April 27, 2004: FDA/EPA recommends pregnant women to restrict their fish consumption because of methylmercury content

last time modified: July 10,  2008

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