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Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study

BACKGROUND: In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of ox...

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Autores principales: Osthoff, Michael, Dean, Melinda M., Baird, Paul N., Richardson, Andrea J., Daniell, Mark, Guymer, Robyn H., Eisen, Damon P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514807/
https://www.ncbi.nlm.nih.gov/pubmed/26207622
http://dx.doi.org/10.1371/journal.pone.0134107
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author Osthoff, Michael
Dean, Melinda M.
Baird, Paul N.
Richardson, Andrea J.
Daniell, Mark
Guymer, Robyn H.
Eisen, Damon P.
author_facet Osthoff, Michael
Dean, Melinda M.
Baird, Paul N.
Richardson, Andrea J.
Daniell, Mark
Guymer, Robyn H.
Eisen, Damon P.
author_sort Osthoff, Michael
collection PubMed
description BACKGROUND: In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and severity of AMD. METHODS: MBL levels and single nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were determined in 109 patients with AMD and 109 age- and sex-matched controls. RESULTS: MBL expression levels were equally distributed in both cases (early and late AMD) and controls (p>0.05). However, there was a trend towards higher median MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4 μg/ml, p = 0.09) and MBL deficiency (<0.5 μg/ml) was encountered less frequently in the late AMD group (35% vs 56%, p = 0.03). FCN2 and MBL2 allele frequencies were similarly distributed in early and late AMD cases compared with controls (p>0.05 for all analyses) as were MBL2 genotypes. Similarly, there was no significant difference in allele frequencies in any SNPs in either the MBL2 or FCN2 gene in cases with early vs. late AMD. CONCLUSIONS: SNPs of lectin pathway proteins investigated in this study were not associated with AMD or AMD severity. However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity.
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spelling pubmed-45148072015-07-29 Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study Osthoff, Michael Dean, Melinda M. Baird, Paul N. Richardson, Andrea J. Daniell, Mark Guymer, Robyn H. Eisen, Damon P. PLoS One Research Article BACKGROUND: In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and severity of AMD. METHODS: MBL levels and single nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were determined in 109 patients with AMD and 109 age- and sex-matched controls. RESULTS: MBL expression levels were equally distributed in both cases (early and late AMD) and controls (p>0.05). However, there was a trend towards higher median MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4 μg/ml, p = 0.09) and MBL deficiency (<0.5 μg/ml) was encountered less frequently in the late AMD group (35% vs 56%, p = 0.03). FCN2 and MBL2 allele frequencies were similarly distributed in early and late AMD cases compared with controls (p>0.05 for all analyses) as were MBL2 genotypes. Similarly, there was no significant difference in allele frequencies in any SNPs in either the MBL2 or FCN2 gene in cases with early vs. late AMD. CONCLUSIONS: SNPs of lectin pathway proteins investigated in this study were not associated with AMD or AMD severity. However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity. Public Library of Science 2015-07-24 /pmc/articles/PMC4514807/ /pubmed/26207622 http://dx.doi.org/10.1371/journal.pone.0134107 Text en © 2015 Osthoff et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Osthoff, Michael
Dean, Melinda M.
Baird, Paul N.
Richardson, Andrea J.
Daniell, Mark
Guymer, Robyn H.
Eisen, Damon P.
Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study
title Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study
title_full Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study
title_fullStr Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study
title_full_unstemmed Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study
title_short Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study
title_sort association study of mannose-binding lectin levels and genetic variants in lectin pathway proteins with susceptibility to age-related macular degeneration: a case-control study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514807/
https://www.ncbi.nlm.nih.gov/pubmed/26207622
http://dx.doi.org/10.1371/journal.pone.0134107
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