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

This study was aimed at evaluating the changes in metallothionein (MT) concentration in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartments. The impact of single-nucleotide polymor...

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Main Authors: Milena Ściskalska, Monika Ołdakowska, Halina Milnerowicz
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/11/5725
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author Milena Ściskalska
Monika Ołdakowska
Halina Milnerowicz
author_facet Milena Ściskalska
Monika Ołdakowska
Halina Milnerowicz
author_sort Milena Ściskalska
collection DOAJ
description This study was aimed at evaluating the changes in metallothionein (MT) concentration in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartments. The impact of single-nucleotide polymorphisms (SNPs) in the <i>MT1A</i> (rs11640851), <i>MT1B</i> (rs964372) and <i>MT2A</i> (rs10636) genes on MT concentration and their association with the concentration of metals (Cu, Zn, Cd) and ceruloplasmin as Cu-related proteins were analyzed. The concentration of a high-sensitivity C-reactive protein (hs-CRP) and IL-6 as markers of inflammation, and malonyldialdehyde (MDA), superoxide dismutase (SODs) activity and the value of total antioxidant capacity (TAC) as parameters describing the pro/antioxidative balance were also assessed. In the AP patient groups, an increased MT concentration in erythrocyte lysate compared to healthy subjects was shown, especially in individuals with the GG genotype for rs964372 in the <i>MT1B</i> gene. A Zn concentration was especially decreased in the blood of smoking AP patients with the AA genotype for SNP rs11640851 in the <i>MT1A</i> gene and the GC genotype for SNP rs10636 in MT2A, compared to non-smokers with AP, which was accompanied by an increase in the value of the Cu/Zn ratio. The exposure to tobacco smoke xenobiotics increased the risk of AP occurrence in subjects with the CC genotype for SNP rs11640851 in the <i>MT1A</i> gene by more than fourfold. The investigated polymorphisms, rs11640851 in the <i>MT1A</i> gene, rs964372 in the <i>MT1B</i> gene and rs10636 in the <i>MT2A</i> gene, seem to be an important factor in maintaining homeostasis in an organism under oxidative stress conditions.
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spelling doaj.art-749a3b7ea0204a88a71b64cbd45470512023-11-21T21:38:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211572510.3390/ijms22115725Importance of Genetic Polymorphisms in <i>MT1</i> and <i>MT2</i> Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers—Preliminary FindingsMilena Ściskalska0Monika Ołdakowska1Halina Milnerowicz2Department of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, PolandDepartment of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, PolandDepartment of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, PolandThis study was aimed at evaluating the changes in metallothionein (MT) concentration in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartments. The impact of single-nucleotide polymorphisms (SNPs) in the <i>MT1A</i> (rs11640851), <i>MT1B</i> (rs964372) and <i>MT2A</i> (rs10636) genes on MT concentration and their association with the concentration of metals (Cu, Zn, Cd) and ceruloplasmin as Cu-related proteins were analyzed. The concentration of a high-sensitivity C-reactive protein (hs-CRP) and IL-6 as markers of inflammation, and malonyldialdehyde (MDA), superoxide dismutase (SODs) activity and the value of total antioxidant capacity (TAC) as parameters describing the pro/antioxidative balance were also assessed. In the AP patient groups, an increased MT concentration in erythrocyte lysate compared to healthy subjects was shown, especially in individuals with the GG genotype for rs964372 in the <i>MT1B</i> gene. A Zn concentration was especially decreased in the blood of smoking AP patients with the AA genotype for SNP rs11640851 in the <i>MT1A</i> gene and the GC genotype for SNP rs10636 in MT2A, compared to non-smokers with AP, which was accompanied by an increase in the value of the Cu/Zn ratio. The exposure to tobacco smoke xenobiotics increased the risk of AP occurrence in subjects with the CC genotype for SNP rs11640851 in the <i>MT1A</i> gene by more than fourfold. The investigated polymorphisms, rs11640851 in the <i>MT1A</i> gene, rs964372 in the <i>MT1B</i> gene and rs10636 in the <i>MT2A</i> gene, seem to be an important factor in maintaining homeostasis in an organism under oxidative stress conditions.https://www.mdpi.com/1422-0067/22/11/5725cadmiumcopperzincmetallothioneinsingle-nucleotide polymorphismrs11640851
spellingShingle Milena Ściskalska
Monika Ołdakowska
Halina Milnerowicz
Importance of Genetic Polymorphisms in <i>MT1</i> and <i>MT2</i> Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers—Preliminary Findings
International Journal of Molecular Sciences
cadmium
copper
zinc
metallothionein
single-nucleotide polymorphism
rs11640851
title Importance of Genetic Polymorphisms in <i>MT1</i> and <i>MT2</i> Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers—Preliminary Findings
title_full Importance of Genetic Polymorphisms in <i>MT1</i> and <i>MT2</i> Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers—Preliminary Findings
title_fullStr Importance of Genetic Polymorphisms in <i>MT1</i> and <i>MT2</i> Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers—Preliminary Findings
title_full_unstemmed Importance of Genetic Polymorphisms in <i>MT1</i> and <i>MT2</i> Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers—Preliminary Findings
title_short Importance of Genetic Polymorphisms in <i>MT1</i> and <i>MT2</i> Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers—Preliminary Findings
title_sort importance of genetic polymorphisms in i mt1 i and i mt2 i genes in metals homeostasis and their relationship with the risk of acute pancreatitis occurrence in smokers preliminary findings
topic cadmium
copper
zinc
metallothionein
single-nucleotide polymorphism
rs11640851
url https://www.mdpi.com/1422-0067/22/11/5725
work_keys_str_mv AT milenasciskalska importanceofgeneticpolymorphismsinimt1iandimt2igenesinmetalshomeostasisandtheirrelationshipwiththeriskofacutepancreatitisoccurrenceinsmokerspreliminaryfindings
AT monikaołdakowska importanceofgeneticpolymorphismsinimt1iandimt2igenesinmetalshomeostasisandtheirrelationshipwiththeriskofacutepancreatitisoccurrenceinsmokerspreliminaryfindings
AT halinamilnerowicz importanceofgeneticpolymorphismsinimt1iandimt2igenesinmetalshomeostasisandtheirrelationshipwiththeriskofacutepancreatitisoccurrenceinsmokerspreliminaryfindings