title: The effect of metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues.
abstract: Metallothioneins (MTs) are intracellular thiol-rich heavy metal-binding proteins which join trace metal ions protecting cells against heavy metal toxicity and regulate metal distribution and donation to various enzymes and transcription factors. The goal of this study was to identify the -5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene, and to investigate its effect on allele-specific gene expression and Cd, Zn, Cu and Ni content in sinonasal inverted papilloma tissue (IP), with non-cancerous sinonasal mucosa (NCM) as a control. The MT2A promoter region -5 A/G SNP was identified by restriction fragment length polymorphism using 117 IP and 132 NCM. MT2A gene analysis was performed by quantitative real-time PCR. Metal levels were analyzed by flame atomic absorption spectrometry. The frequency of A allele carriage was 99.2% and 100% in IP and NCM, respectively. The G allele carriage was detected in 23.9% of IP and in 12.1% of the NCM samples. As a result, a significant association of -5 A/G SNP in MT2A gene with mRNA expression in both groups was determined. A significant association was identified between the -5 A/G SNP in the MT2A gene with mRNA expression in both groups. A highly significant association was detected between the rs28366003 genotype and Cd and Zn content in IP. Furthermore, significant differences were identified between A/A and A/G genotype with regard to the type of metal contaminant. The Spearman rank correlation results showed the MT2A gene expression and both Cd and Cu levels were negatively correlated. The results obtained in this study suggest that the -5 A/G SNP in the MT2A gene may have an effect on allele-specific gene expression and toxic metal accumulation in sinonasal inverted papilloma.
authors.affiliation: I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153 Łódź, Poland. Electronic address: katarzyna.starska@umed.lodz.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Starska
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bryś
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Forma
authors.affiliation: II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź, Poland.
authors.forename: Jurek
authors.initials: J
authors.lastname: Olszewski
authors.affiliation: II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Pietkiewicz
authors.affiliation: Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Lewy-Trenda
authors.affiliation: Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland.
authors.forename: Marian
authors.initials: M
authors.lastname: Danilewicz
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Krześlak
mesh_terms: D000368:Aged; D000483:Alleles; D002104:Cadmium / Q000378:metabolism; D016022:Case-Control Studies; D003300:Copper / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D019216:Metals, Heavy / Q000378:metabolism*; D008875:Middle Aged; D009669:Nose Neoplasms / Q000235:genetics*; D018308:Papilloma, Inverted / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D013054:Spectrophotometry, Atomic; D015032:Zinc / Q000378:metabolism
chemical_list: C491053:MT2A protein, human; D019216:Metals, Heavy; D002104:Cadmium; D003300:Copper; D008668:Metallothionein; D015032:Zinc
keywords: Heavy metals; Metallothionein 2A (MT2A); Single-nucleotide polymorphism (SNP); Sinonasal inverted papilloma