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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MDPI AG
2021-05-01
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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 |