Polymorphism of Metallothionein 2A Modifies Lead Body Burden in Workers Chronically Exposed to the Metal

Abstract

Lead (Pb) is a metal that accumulates in the human body, inducing several adverse health effects. One of the proteins responsible for the distribution of metal in the body is metallothionein (MT), which is expressed by different genes, and it is supposed that genetic variation in the genes that encode MTs may affect the Pb body burden. The present study aimed to evaluate the genetic effects of the polymorphism of MT2A (single nucleotide polymorphism rs10636; C→G) on blood Pb levels (BLL) of workers from car battery factories who are chronically exposed to the metal. In total, 221 men participated in the study; genomic DNA from whole blood was extracted, and genotyping of MT2A was performed by TaqMan assays; BLL were quantified by inductively coupled plasma mass spectrometry (ICP-MS). BLL were 25 ± 14 µg/dl (range 1.9-68); BLL were positively correlated with duration of work and smoking status. Individuals who carried at least one C allele had higher BLL than those with the GG genotype (β = -0.45; p = 0.025, multivariable linear regression analyses). Taken together, our data support the hypothesis that polymorphisms in genes related to the transport of Pb, such as MTs, may modulate the concentrations of the metal in the body and, consequently, adverse health effects induced by Pb exposure.

The Metals in the Biological Periodic System of the Elements: Concepts and Conjectures

“…For example, an Asn27Thr substitution in metallothionein-1A affects its zinc-binding capacity and together with polymorphisms of other human metallothionein genes is associated with the risk of developing type 2 diabetes, coronary heart disease, and other complications of diabetes [ 22 , 23 ] and with altered metabolism of toxic metal ions, i.e. , cadmium, lead, and mercury [ 24 , 25 , 26 ]. Levels for toxic metals in blood are associated with polymorphisms in metal transporter genes and other genes, thus providing further evidence that subsets of individuals are more susceptible to the toxic effects of some metal ions [ 27 ].…”

Exposure to Toxic Heavy Metals Can Influence Homocysteine Metabolism?

“…The deleterious effect of Pb depends on the exposure period, received dose, route of absorption (respiratory system, digestive system and/or skin), presence of other xenobiotics, age, sex, and genetic factors [35]. After absorption by inhalation, Pb penetrates directly into the circulatory system [13]. In contrast, after entering through the gastrointestinal tract, Pb is absorbed into the stomach and small intestine and transported first into the liver and then into the general circulation [36].…”

Ecogenetics of lead toxicity and its influence on risk assessment

“…49 Recently, it was reported that individuals occupationally exposed to Pb who are polymorphic for MT2A rs10636 GG genotype is associated with higher Pb-B level. 128 Several studies like these however report variations in outcome and continues to be ambiguous. is transported via ferroportin (Fpn1) into the plasma where it gets oxidized back to Fe 3þ and binds to transferrin (TF).…”