Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders

Background: Synthesis of thyroid hormones and regulation of their metabolism involve free radicals that may affect redox balance in the body. Thyroid disorders causing variations in the levels of thyroid hormones may alter cellular oxidative stress. The aim of this study was to measure the antioxida...

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Main Authors: Ramli, Nur Siti Fatimah, Junit, Sarni Mat, Ng, Khoon Leong, Razali, Nurhanani, Jayapalan, Jaime Jacqueline, Aziz, Azlina Abdul
Format: Article
Language:English
Published: PeerJ 2017
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Online Access:http://eprints.um.edu.my/19048/1/Analyses_of_antioxidant_status_and_nucleotide_alterations_in_genes_encoding_antioxidant_enzymes_in_patients_with_benign_and_malignant_thyroid_disorders.pdf
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author Ramli, Nur Siti Fatimah
Junit, Sarni Mat
Ng, Khoon Leong
Razali, Nurhanani
Jayapalan, Jaime Jacqueline
Aziz, Azlina Abdul
author_facet Ramli, Nur Siti Fatimah
Junit, Sarni Mat
Ng, Khoon Leong
Razali, Nurhanani
Jayapalan, Jaime Jacqueline
Aziz, Azlina Abdul
author_sort Ramli, Nur Siti Fatimah
collection UM
description Background: Synthesis of thyroid hormones and regulation of their metabolism involve free radicals that may affect redox balance in the body. Thyroid disorders causing variations in the levels of thyroid hormones may alter cellular oxidative stress. The aim of this study was to measure the antioxidant activities and biomarkers of oxidative stress in serum and red blood cells (RBC) of patients with benign and malignant thyroid disorders and to investigate if changes in the antioxidant activities in these patients were linked to alterations in genes encoding the antioxidant enzymes. Methods: Forty-one patients with thyroid disorders from University of Malaya Medical Centre were recruited. They were categorised into four groups: multinodular goitre (MNG) (n = 18), follicular thyroid adenoma (FTA) (n = 7), papillary thyroid cancer (PTC) (n = 10), and follicular thyroid cancer (FTC) (n = 6). Serum and RBC of patients were analysed for antioxidant activities, antioxidant enzymes, and biomarkers of oxidative stress. Alterations in genes encoding the antioxidant enzymes were analysed using whole exome sequencing and PCR-DNA sequencing. Results: Patients with thyroid disorders had significantly higher serum superoxide dismutase (SOD) and catalase (CAT) activities compared to control, but had lower activities in RBC. There were no significant changes in serum glutathione peroxidase (GPx) activity. Meanwhile, GPx activity in RBC was reduced in PTC and FTC, compared to control and the respective benign groups. Antioxidant activities in serum were decreased in the thyroid disorder groups when compared to the control group. The levels of malondialdehyde (MDA) were elevated in the serum of FTA group when compared to controls, while in the RBC, only the MNG and PTC groups showed higher MDA equivalents than control. Serum reactive oxygen species (ROS) levels in PTC group of both serum and RBC were significantly higher than control group. Whole exome sequencing has resulted in identification of 49 single nucleotide polymorphisms (SNPs) in MNG and PTC patients and their genotypic and allelic frequencies were calculated. Analyses of the relationship between serum enzyme activities and the total SNPs identified in both groups revealed no correlation. Discussion: Different forms of thyroid disorders influence the levels of antioxidant status in the serum and RBC of these patients, implying varying capability of preventing oxidative stress. A more comprehensive study with a larger target population should be done in order to further evaluate the relationships between antioxidant enzymes gene polymorphisms and thyroid disorders, as well as strengthening the minor evidences provided in literatures.
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spelling um.eprints-190482019-12-20T07:42:59Z http://eprints.um.edu.my/19048/ Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders Ramli, Nur Siti Fatimah Junit, Sarni Mat Ng, Khoon Leong Razali, Nurhanani Jayapalan, Jaime Jacqueline Aziz, Azlina Abdul R Medicine Background: Synthesis of thyroid hormones and regulation of their metabolism involve free radicals that may affect redox balance in the body. Thyroid disorders causing variations in the levels of thyroid hormones may alter cellular oxidative stress. The aim of this study was to measure the antioxidant activities and biomarkers of oxidative stress in serum and red blood cells (RBC) of patients with benign and malignant thyroid disorders and to investigate if changes in the antioxidant activities in these patients were linked to alterations in genes encoding the antioxidant enzymes. Methods: Forty-one patients with thyroid disorders from University of Malaya Medical Centre were recruited. They were categorised into four groups: multinodular goitre (MNG) (n = 18), follicular thyroid adenoma (FTA) (n = 7), papillary thyroid cancer (PTC) (n = 10), and follicular thyroid cancer (FTC) (n = 6). Serum and RBC of patients were analysed for antioxidant activities, antioxidant enzymes, and biomarkers of oxidative stress. Alterations in genes encoding the antioxidant enzymes were analysed using whole exome sequencing and PCR-DNA sequencing. Results: Patients with thyroid disorders had significantly higher serum superoxide dismutase (SOD) and catalase (CAT) activities compared to control, but had lower activities in RBC. There were no significant changes in serum glutathione peroxidase (GPx) activity. Meanwhile, GPx activity in RBC was reduced in PTC and FTC, compared to control and the respective benign groups. Antioxidant activities in serum were decreased in the thyroid disorder groups when compared to the control group. The levels of malondialdehyde (MDA) were elevated in the serum of FTA group when compared to controls, while in the RBC, only the MNG and PTC groups showed higher MDA equivalents than control. Serum reactive oxygen species (ROS) levels in PTC group of both serum and RBC were significantly higher than control group. Whole exome sequencing has resulted in identification of 49 single nucleotide polymorphisms (SNPs) in MNG and PTC patients and their genotypic and allelic frequencies were calculated. Analyses of the relationship between serum enzyme activities and the total SNPs identified in both groups revealed no correlation. Discussion: Different forms of thyroid disorders influence the levels of antioxidant status in the serum and RBC of these patients, implying varying capability of preventing oxidative stress. A more comprehensive study with a larger target population should be done in order to further evaluate the relationships between antioxidant enzymes gene polymorphisms and thyroid disorders, as well as strengthening the minor evidences provided in literatures. PeerJ 2017 Article PeerReviewed application/pdf en http://eprints.um.edu.my/19048/1/Analyses_of_antioxidant_status_and_nucleotide_alterations_in_genes_encoding_antioxidant_enzymes_in_patients_with_benign_and_malignant_thyroid_disorders.pdf Ramli, Nur Siti Fatimah and Junit, Sarni Mat and Ng, Khoon Leong and Razali, Nurhanani and Jayapalan, Jaime Jacqueline and Aziz, Azlina Abdul (2017) Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders. PeerJ, 5. e3365. ISSN 2167-8359, DOI https://doi.org/10.7717/peerj.3365 <https://doi.org/10.7717/peerj.3365>. http://dx.doi.org/10.7717/peerj.3365 doi:10.7717/peerj.3365
spellingShingle R Medicine
Ramli, Nur Siti Fatimah
Junit, Sarni Mat
Ng, Khoon Leong
Razali, Nurhanani
Jayapalan, Jaime Jacqueline
Aziz, Azlina Abdul
Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders
title Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders
title_full Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders
title_fullStr Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders
title_full_unstemmed Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders
title_short Analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders
title_sort analyses of antioxidant status and nucleotide alterations in genes encoding antioxidant enzymes in patients with benign and malignant thyroid disorders
topic R Medicine
url http://eprints.um.edu.my/19048/1/Analyses_of_antioxidant_status_and_nucleotide_alterations_in_genes_encoding_antioxidant_enzymes_in_patients_with_benign_and_malignant_thyroid_disorders.pdf
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