## 3 Human Genetic Diversity
### MeHg Exposure and Human Genetic Diversity  
The majority of ingested MeHg passes into the bloodstream, by which route it reaches all tissues. Here, MeHg enters cells thanks to its ability to form water-soluble complexes with the amino acid cysteine. After forming a complex with reduced glutathione (GSH) (Figure 1), MeHg is excreted by the liver cells into the bile. At this point, the glutathione is hydrolyzed, leading to the release of the methylmercury-cysteine complex. The latter is mostly secreted into the intestine tract, where MeHg is demethylated by intestine microflora. The resulting inorganic Hg is then eliminated via the feces [70]. \begin{table}
\begin{tabular}{c c c c} \hline
**Study** & **Genes** & **Biomarker** & **Sample** \\ \hline \hline \multirow{3}{*}{[50]} & & & Swedish cases of acute \\  & & & myocardial infarction/stroke and \\  & & & controls \\ \hline
[51] & GSTM1; GSTT1 & Hair Hg & Students in Austria \\ \hline
[52] & GCLM; GSTP1 & Erythrocyte Hg & Fish-eating Swedish individuals \\ \hline
[53] & GSTP1; MT4; GSTM1; & Blood and hair Hg & Students in Austria \\  & GCLC; GSTT1 & Maternal and cord blood Hg & Korean mothers and their infants \\ \hline
[54] & GSTM1; GSS; GSTP1; SEPT1 & Hair and urinary Hg & Michigan dental professionals \\ \hline
[56] & MT1M; MT2A; MT1A & Hair and urinary Hg & Michigan dental professionals \\ \hline
[57] & APOE & Cord blood Hg & Children in Taiwan \\ \hline
[58] & GCLM; GSTM1 & Blood and hair Hg &
\begin{tabular}{c} Amazonian population in Brazil \\ chronically exposed to MeHg \\ from fish \\ \end{tabular} \\ \hline
[59] & TF & Umbilical cord Hg & Children from Bristol \\ \hline
[60] & GCLC; GCLM; GSTM1 & \
\begin{tabular}{c} Plasmatic Hg and MeHg; \\ whole blood Hg \\ \end{tabular} &
\begin{tabular}{c} Fish-eating communities of \\ Brazilian Amazon \\ \end{tabular} \\ \hline
[61] & ABCB1; ABCC1; ABCC2 & Cord blood Hg &
\begin{tabular}{c} Pregnant women from Greece, \\ Italy and Spain \\ \end{tabular} \\ \hline
[62] & APOE & Cord blood Hg & Children in Taiwan \\ \hline
[63] & ABCB1; ABCC1; ABCC2 & Hair Hg &
\begin{tabular}{c} Seychellois mother–child pairs with a \\ diet rich in fish of mixed African, \\ European and East Asian origin \\ \end{tabular} \\ \hline
[64] & GLRX2; GSTA4; GSTM3; GSTO1; & \\  & SELS; MT1M; (see Table S1 for the & Blood and urinary Hg & American dental professionals \\ whole list) & & \\ \hline
[65] & CBS; TXNRD2; SEPHS2; CYP1A2; & \\  & CBS; MTRR; (see Table S1 for the & Blood Hg & Inuit from Canada \\ whole list) & & \\ \hline
[66] & GCLC; GCLM; GSTP1 & \
\begin{tabular}{c} Maternal blood and hair Hg \\ and cord blood Hg \\ \end{tabular} &
\begin{tabular}{c} Seychellois mother–child pairs with a \\ diet rich in fish of mixed African, \\ European and East Asian origin \\ \end{tabular} \\ \hline
[67] & BDNF; GSTP1 & Hair Hg & Children in Valentia \\ \hline \hline \end{tabular}
\end{table} 
Table 1: List of epidemiological studies investigating the influence of genetic polymorphisms on MeHg toxicokinetic. Genes in which the above polymorphisms were identified, biomarkers affected, and samples studied are shown for each study. In recent years, epidemiological studies on populations exposed to MeHg have been showing that several genes mediating the toxicokinetics of Hg are polymorphic in humans, and may influence inter-individual variability in Hg exposure biomarker values and health outcomes (Tables 1 and S1 for further details). In line with this, as demonstrated by kinetic studies, MeHg half-life, which is a direct determinant of the Hg body burden [71], can vary widely in humans, which may be due also to a naturally occurring biological basis for the variation in MeHg toxicokinetics.