Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

Abstract

Background Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might therefore influence excretion of these metals. Methods 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 was associated with lower urinary Cd. Conclusions These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion.

Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

“…Two pathway models were proposed to explain the binding of Zn/Cd ions to MT, either by cooperative or non-cooperative binding 32 . Experimental evidence showed that the first four Cd metallic ions that replaced Zn ions were all in the alpha domain; however, it was also possible that several intermediate states occurred that could involve the β domain 33 , 34 . Assuming that the superior electronegativity of Pt ions would replace Zn in a similar fashion to Cd ions, the 3D structures of MT3-Pt/Zn complexes could be equivalent to those containing Cd ions, as shown in Fig.…”

lncRNA OTUD6B-AS1 Exacerbates As2O3-Induced Oxidative Damage in Bladder Cancer via miR-6734-5p-Mediated Functional Inhibition of IDH2

“…Accumulated evidence supports the regulation of lncRNA transcription by multiple factors, including toxic heavy metals, plant extracts, and chemotherapeutic drugs [ 41 ]. MTF1, a transcription factor, drives mRNA expression in response to toxic heavy metals [ 42 ]. van Loo et al previously demonstrated that zinc regulates a key transcriptional pathway involved in epileptogenesis via MTF1 [ 43 ].…”

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

“…The frequencies of the GG genotype range from 42.9 % in Chinese (115) to 67.7 % in healthy Spanish population (97). Healthy Chinese population had the highest percentage of the CC genotype (9.7 %) (115), whereas the US and Polish populations had the lowest frequency (about 4.0 %) (82,104). The only study that reported genotype frequencies of the rs10636 SNP in children was in boys and girls with the mean age of 10 years in Portugal, a country known for increased Hg intake through seafood/fish consumption and the risk of related neurotoxic effects in both sexes at young age (116).…”