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Effect of Lysyl Oxidase G473A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis

BACKGROUND: Oral submucous fibrosis (OSF) is a debilitating collagen-metabolic disorder leading to submucosal fibrosis and trismus. Lysyl oxidase (LOX), a critical collagen biosynthetic enzyme, is up-regulated in OSF. Polymorphisms in the Lysyl oxidase gene have been associated with increased risk o...

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Autores principales: Mukherjee, Sanjit, Katarkar, Atul, Dhariwal, Richa, Mohanty, Sweta, Mahato, Basudev, Ray, Jay Gopal, Chaudhuri, Keya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629460/
https://www.ncbi.nlm.nih.gov/pubmed/34452563
http://dx.doi.org/10.31557/APJCP.2021.22.8.2493
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author Mukherjee, Sanjit
Katarkar, Atul
Dhariwal, Richa
Mohanty, Sweta
Mahato, Basudev
Ray, Jay Gopal
Chaudhuri, Keya
author_facet Mukherjee, Sanjit
Katarkar, Atul
Dhariwal, Richa
Mohanty, Sweta
Mahato, Basudev
Ray, Jay Gopal
Chaudhuri, Keya
author_sort Mukherjee, Sanjit
collection PubMed
description BACKGROUND: Oral submucous fibrosis (OSF) is a debilitating collagen-metabolic disorder leading to submucosal fibrosis and trismus. Lysyl oxidase (LOX), a critical collagen biosynthetic enzyme, is up-regulated in OSF. Polymorphisms in the Lysyl oxidase gene have been associated with increased risk of OSF and might affect normal collagen synthesis, accumulation, or degradation, crucial in determining fibrosis severity. METHODS: One hundred OSF cases and 100 controls were genotyped for LOX G473A(Arg158Gln) polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The expression of LOX was estimated both by quantitative mRNA analysis and western blot. Total soluble collagen was evaluated from mucosal tissue obtained from OSF cases. Immunohistochemical (IHC) localization of type 1 collagen was performed in mucosal tissue obtained from patients carrying various genotypes. RESULTS: Heterozygous G473A genotype was significantly higher in OSF cases [2.063(95% CI =1.059-4.016)], among 26-40 years age-group [4.375(95% CI=1.323-14.267),p=0.029] and in male patients [2.38 (95% CI= 1.107-5.121), p= 0.042]. LOX expression was significantly higher in cases of the heterozygous or homozygous carrier (p<0.001). We found the total soluble collagen level significantly (p<0.001) higher among patients carrying GA or AA genotype. IHC revealed focal deposition of type1 collagen in the submucosal tissue; comparatively higher deposition was evident in mucosal tissue of OSF patients carrying AA genotype. CONCLUSIONS: These findings suggest LOX G473A polymorphism confers an increased risk of OSF and may affect collagen accumulation in OSF cases.
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spelling pubmed-86294602021-12-03 Effect of Lysyl Oxidase G473A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis Mukherjee, Sanjit Katarkar, Atul Dhariwal, Richa Mohanty, Sweta Mahato, Basudev Ray, Jay Gopal Chaudhuri, Keya Asian Pac J Cancer Prev Research Article BACKGROUND: Oral submucous fibrosis (OSF) is a debilitating collagen-metabolic disorder leading to submucosal fibrosis and trismus. Lysyl oxidase (LOX), a critical collagen biosynthetic enzyme, is up-regulated in OSF. Polymorphisms in the Lysyl oxidase gene have been associated with increased risk of OSF and might affect normal collagen synthesis, accumulation, or degradation, crucial in determining fibrosis severity. METHODS: One hundred OSF cases and 100 controls were genotyped for LOX G473A(Arg158Gln) polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The expression of LOX was estimated both by quantitative mRNA analysis and western blot. Total soluble collagen was evaluated from mucosal tissue obtained from OSF cases. Immunohistochemical (IHC) localization of type 1 collagen was performed in mucosal tissue obtained from patients carrying various genotypes. RESULTS: Heterozygous G473A genotype was significantly higher in OSF cases [2.063(95% CI =1.059-4.016)], among 26-40 years age-group [4.375(95% CI=1.323-14.267),p=0.029] and in male patients [2.38 (95% CI= 1.107-5.121), p= 0.042]. LOX expression was significantly higher in cases of the heterozygous or homozygous carrier (p<0.001). We found the total soluble collagen level significantly (p<0.001) higher among patients carrying GA or AA genotype. IHC revealed focal deposition of type1 collagen in the submucosal tissue; comparatively higher deposition was evident in mucosal tissue of OSF patients carrying AA genotype. CONCLUSIONS: These findings suggest LOX G473A polymorphism confers an increased risk of OSF and may affect collagen accumulation in OSF cases. West Asia Organization for Cancer Prevention 2021-08 /pmc/articles/PMC8629460/ /pubmed/34452563 http://dx.doi.org/10.31557/APJCP.2021.22.8.2493 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mukherjee, Sanjit
Katarkar, Atul
Dhariwal, Richa
Mohanty, Sweta
Mahato, Basudev
Ray, Jay Gopal
Chaudhuri, Keya
Effect of Lysyl Oxidase G473A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis
title Effect of Lysyl Oxidase G473A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis
title_full Effect of Lysyl Oxidase G473A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis
title_fullStr Effect of Lysyl Oxidase G473A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis
title_full_unstemmed Effect of Lysyl Oxidase G473A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis
title_short Effect of Lysyl Oxidase G473A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis
title_sort effect of lysyl oxidase g473a polymorphism on lysyl oxidase and total soluble collagen expression in oral submucous fibrosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629460/
https://www.ncbi.nlm.nih.gov/pubmed/34452563
http://dx.doi.org/10.31557/APJCP.2021.22.8.2493
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