Metallothionein 2A gene polymorphisms in relation to diseases and trace element levels in humans

Abstract

Human metallothioneins are a superfamily of low molecular weight intracellular proteins, whose synthesis can be induced by essential elements (primarily Zn and Cu), toxic elements and chemical agents, and stress-producing conditions. Of the four known isoforms in the human body MT2 is the most common. The expression of metallothioneins is encoded by a multigene family of linked genes and can be influenced by single nucleotide polymorphisms (SNPs) in these genes. To date, 24 SNPs in the MT2A gene have been identified with the incidence of about 1 % in various population groups, and three of them were shown to affect physiological and pathophysiological processes. This review summarises current knowledge about these three SNPs in the MT2A gene and their associations with element concentrations in the body of healthy and diseased persons. The most investigated SNP is rs28366003 (MT2A −5 A/G). Reports associate it with longevity, cancer (breast, prostate, laryngeal, and in paranasal sinuses), and chronic renal disease. The second most investigated SNP, rs10636 (MT2A +838G/C), is associated with breast cancer, cardiovascular disease, and type 2 diabetes. Both are also associated with several metal/metalloid concentrations in the organism. The third SNP, rs1610216 (MT2A −209A/G), has been studied for association with type 2 diabetes, cardiomyopathy, hyperglycaemia, and Zn concentrations. Metallothionein concentrations and MT2A polymorphisms have a potential to be used as biomarkers of metal exposure and clinical markers of a number of chronic diseases. This potential needs to be studied and verified in a large number of well-defined groups of participants (several hundreds and thousands) with a focus on particular physiological or pathological condition and taking into consideration other contributing factors, such as environmental exposure and individual genetic and epigenetic makeup.

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

“…Its additional important role is scavenging free radicals generated in oxidative stress and detoxification. Due to many -SH groups and high affinity/high capacity to bind various reactive metal ions, such as Cd, mercury (Hg), Cu, Pb, nickel (Ni), cobalt (Co), iron (Fe), silver (Ag) and gold (Au), MT contribute to their decreased availability for toxic effects in conditions of acute exposure, whereas in conditions of chronic exposure accumulated toxic metals (such as Cd-MT or Hg-MT complex) may pose a risk for toxic effects (reviewed in [21,22]). Tobacco smoking can affect MT expression in the placenta and subsequent binding, transfer and placental accumulation of related metal ions.…”

Replicated, urban-driven exposure to metallic trace elements in two passerines

“…feathers and skin) 72 , 82 and are positively selected in environments polluted with MTEs 72 , 82 – 84 . Consequently, comparing phenotypic traits (e.g., tegument melanin-based colouration, MTE gastro-intestinal absorption rates, antioxidative response, metallothionein expression) and allele frequency at loci associated with the metabolism of MTEs ( e.g., GCLC , GCLM and MT2A genes) 85 , 86 along replicated urbanization gradients appears as a promising opportunity to study parallel evolution mediated by urbanization 17 .…”

Importance of Genetic Polymorphisms in MT1 and MT2 Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers—Preliminary Findings

“…Numerous reports have confirmed the relationship between SNP rs10636 in the MT2A gene and the concentration of metals in the blood [ 5 , 29 , 47 ]. The studies conducted by Kayaalti et al showed a significant decrease in the concentration of Zn in the blood of healthy people with the GG genotype for SNP rs10636 in the MT2A gene [ 36 ].…”