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Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity

The results of many studies indicate that cadmium (Cd) exposure is harmful to humans, with the proximal tubule of the kidney being the main target of Cd accumulation and toxicity. Studies have also shown that Cd has the effect of activating the pathway of epidermal growth factor receptor (EGFR) sign...

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Autores principales: Lin, Chun-Ting, Chen, Ting-Hao, Yang, Chen-Cheng, Luo, Kuei-Hau, Chen, Tzu-Hua, Chuang, Hung-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535213/
https://www.ncbi.nlm.nih.gov/pubmed/34680968
http://dx.doi.org/10.3390/genes12101573
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author Lin, Chun-Ting
Chen, Ting-Hao
Yang, Chen-Cheng
Luo, Kuei-Hau
Chen, Tzu-Hua
Chuang, Hung-Yi
author_facet Lin, Chun-Ting
Chen, Ting-Hao
Yang, Chen-Cheng
Luo, Kuei-Hau
Chen, Tzu-Hua
Chuang, Hung-Yi
author_sort Lin, Chun-Ting
collection PubMed
description The results of many studies indicate that cadmium (Cd) exposure is harmful to humans, with the proximal tubule of the kidney being the main target of Cd accumulation and toxicity. Studies have also shown that Cd has the effect of activating the pathway of epidermal growth factor receptor (EGFR) signaling and cell growth. The EGFR is a family of transmembrane receptors, which are widely expressed in the human kidney. The aim of this study was to investigate the kidney function estimated glomerular filtration rate (eGFR), and its relationship with plasma Cd level and EGFR gene polymorphism. Using data from Academia Sinica Taiwan biobank, 489 subjects aged 30–70 years were analyzed. The demographic characteristics was determined from questionnaires, and biological sampling of urine and blood was determined from physical examination. Kidney function was assessed by the eGFR with CKD-EPI formula. Plasma Cd (ug/L) was measured by inductively coupled plasma mass spectrometry. A total of 97 single-nucleotide polymorphisms (SNPs) were identified in the EGFR on the Taiwan biobank chip, however 4 SNPs did not pass the quality control. Multiple regression analyses were performed to achieve the study aim. The mean (±SD) plasma Cd level of the study subjects was 0.02 (±0.008) ug/L. After adjusting for confounding variables, rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA types had higher eGFR (4.89 mL/min/1.73 m(2) (p = 0.035), 5.54 mL/min/1.73 m(2) (p = 0.03), 4.96 mL/min/1.73 m(2) (p = 0.048) and 5.16 mL/min/1.73 m(2) (p = 0.048), respectively). Plasma cadmium and rs845555 had an interactive effect on eGFR. In conclusion, EGFR polymorphisms could be modifiers of Cd kidney toxicity, in which rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA may be protective, and Cd interacting with rs845555 may affect kidney function.
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spelling pubmed-85352132021-10-23 Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity Lin, Chun-Ting Chen, Ting-Hao Yang, Chen-Cheng Luo, Kuei-Hau Chen, Tzu-Hua Chuang, Hung-Yi Genes (Basel) Article The results of many studies indicate that cadmium (Cd) exposure is harmful to humans, with the proximal tubule of the kidney being the main target of Cd accumulation and toxicity. Studies have also shown that Cd has the effect of activating the pathway of epidermal growth factor receptor (EGFR) signaling and cell growth. The EGFR is a family of transmembrane receptors, which are widely expressed in the human kidney. The aim of this study was to investigate the kidney function estimated glomerular filtration rate (eGFR), and its relationship with plasma Cd level and EGFR gene polymorphism. Using data from Academia Sinica Taiwan biobank, 489 subjects aged 30–70 years were analyzed. The demographic characteristics was determined from questionnaires, and biological sampling of urine and blood was determined from physical examination. Kidney function was assessed by the eGFR with CKD-EPI formula. Plasma Cd (ug/L) was measured by inductively coupled plasma mass spectrometry. A total of 97 single-nucleotide polymorphisms (SNPs) were identified in the EGFR on the Taiwan biobank chip, however 4 SNPs did not pass the quality control. Multiple regression analyses were performed to achieve the study aim. The mean (±SD) plasma Cd level of the study subjects was 0.02 (±0.008) ug/L. After adjusting for confounding variables, rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA types had higher eGFR (4.89 mL/min/1.73 m(2) (p = 0.035), 5.54 mL/min/1.73 m(2) (p = 0.03), 4.96 mL/min/1.73 m(2) (p = 0.048) and 5.16 mL/min/1.73 m(2) (p = 0.048), respectively). Plasma cadmium and rs845555 had an interactive effect on eGFR. In conclusion, EGFR polymorphisms could be modifiers of Cd kidney toxicity, in which rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA may be protective, and Cd interacting with rs845555 may affect kidney function. MDPI 2021-10-02 /pmc/articles/PMC8535213/ /pubmed/34680968 http://dx.doi.org/10.3390/genes12101573 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Chun-Ting
Chen, Ting-Hao
Yang, Chen-Cheng
Luo, Kuei-Hau
Chen, Tzu-Hua
Chuang, Hung-Yi
Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity
title Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity
title_full Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity
title_fullStr Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity
title_full_unstemmed Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity
title_short Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity
title_sort epidermal growth factor receptor (egfr) gene polymorphism may be a modifier for cadmium kidney toxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535213/
https://www.ncbi.nlm.nih.gov/pubmed/34680968
http://dx.doi.org/10.3390/genes12101573
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