Effect of Lysyl Oxidase G473 A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis.
Adolescent
Adult
Case-Control Studies
Child
Child, Preschool
Collagen
/ metabolism
Female
Follow-Up Studies
Genetic Predisposition to Disease
Humans
India
/ epidemiology
Infant
Infant, Newborn
Male
Oral Submucous Fibrosis
/ epidemiology
Polymorphism, Single Nucleotide
Prognosis
Protein-Lysine 6-Oxidase
/ genetics
Risk Factors
Young Adult
Oral submucous fibrosis
Single nucleotide polymorphism
collagen
lysyl oxidase
Journal
Asian Pacific journal of cancer prevention : APJCP
ISSN: 2476-762X
Titre abrégé: Asian Pac J Cancer Prev
Pays: Thailand
ID NLM: 101130625
Informations de publication
Date de publication:
01 Aug 2021
01 Aug 2021
Historique:
received:
05
04
2021
entrez:
28
8
2021
pubmed:
29
8
2021
medline:
18
1
2022
Statut:
epublish
Résumé
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. 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. 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. These findings suggest LOX G473A polymorphism confers an increased risk of OSF and may affect collagen accumulation in OSF cases.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
These findings suggest LOX G473A polymorphism confers an increased risk of OSF and may affect collagen accumulation in OSF cases.
Identifiants
pubmed: 34452563
doi: 10.31557/APJCP.2021.22.8.2493
pmc: PMC8629460
pii:
doi:
Substances chimiques
Collagen
9007-34-5
LOX protein, human
EC 1.4.3.13
Protein-Lysine 6-Oxidase
EC 1.4.3.13
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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