The impact of genetic variation on metabolism of heavy metals: Genetic predisposition?

Abstract

Genetic variations can be considered as internal contributing factors in susceptibility of individuals to heavy metals related toxicities. However, the exact mechanism of such inherent factors in body response to toxic materials, as well as their potentials to be considered as actual susceptibility factors are remaining to be more explored. So far, variations in different genes, which are directly/indirectly involving in the metabolism of heavy metals have been investigated by some experiments. Metallothioneins as one of the well-known groups of enzymes involving in detoxification of heavy metals, were shown to behave differentially among individuals. This phenomenon is due to the presence of some genetic variations in the middle or upper parts of their genomic sequences. The presence of different single nucleotide polymorphisms in metallothionein 2 A gene and the association of these variations with heavy metals body burden have been shown in different populations. Such genetic variations and their potential effects on heavy metal metabolisms and toxicities were shown in other genes, such as divalent metal transporter 1, glutathione related genes and methylenetetrahydrofolate reductase. However, the current data on different populations are challenging because of the presence of various other interference factors like different dietary and life habits, levels of exposure, as well as papulation related factors. Age, sex, smoking, dietary habits, ancestry differences and diverse metal exposure levels are seemed to be other effective variables in this area. In this review, we introduced several potential genes, their studied genetic variations and their impacts on heavy metal body burden, as well as body sensitivity in different populations.