Cargando…

CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation

We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD...

Descripción completa

Detalles Bibliográficos
Autores principales: Vavvas, Demetrios G., Small, Kent W., Awh, Carl C., Zanke, Brent W., Tibshirani, Robert J., Kustra, Rafal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789949/
https://www.ncbi.nlm.nih.gov/pubmed/29311295
http://dx.doi.org/10.1073/pnas.1718059115
_version_ 1783296378197245952
author Vavvas, Demetrios G.
Small, Kent W.
Awh, Carl C.
Zanke, Brent W.
Tibshirani, Robert J.
Kustra, Rafal
author_facet Vavvas, Demetrios G.
Small, Kent W.
Awh, Carl C.
Zanke, Brent W.
Tibshirani, Robert J.
Kustra, Rafal
author_sort Vavvas, Demetrios G.
collection PubMed
description We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD at baseline who had been treated with placebo or the AREDS formulation were evaluated for differences in the risk of progression to NV as a function of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotype groups. We used published genetic grouping: a two-SNP haplotype risk-calling algorithm to assess CFH, and either the single SNP rs10490924 or 372_815del443ins54 to mark ARMS2 risk. Progression risk was determined using the Cox proportional hazard model. Genetics–treatment interaction on NV risk was assessed using a multiiterative bootstrap validation analysis. We identified strong interaction of genetics with AREDS formulation treatment on the development of NV. Individuals with high CFH and no ARMS2 risk alleles and taking the AREDS formulation had increased progression to NV compared with placebo. Those with low CFH risk and high ARMS2 risk had decreased progression risk. Analysis of CFH and ARMS2 genotype groups from a validation dataset reinforces this conclusion. Bootstrapping analysis confirms the presence of a genetics–treatment interaction and suggests that individual treatment response to the AREDS formulation is largely determined by genetics. The AREDS formulation modifies the risk of progression to NV based on individual genetics. Its use should be based on patient-specific genotype.
format Online
Article
Text
id pubmed-5789949
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher National Academy of Sciences
record_format MEDLINE/PubMed
spelling pubmed-57899492018-02-03 CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation Vavvas, Demetrios G. Small, Kent W. Awh, Carl C. Zanke, Brent W. Tibshirani, Robert J. Kustra, Rafal Proc Natl Acad Sci U S A PNAS Plus We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD at baseline who had been treated with placebo or the AREDS formulation were evaluated for differences in the risk of progression to NV as a function of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotype groups. We used published genetic grouping: a two-SNP haplotype risk-calling algorithm to assess CFH, and either the single SNP rs10490924 or 372_815del443ins54 to mark ARMS2 risk. Progression risk was determined using the Cox proportional hazard model. Genetics–treatment interaction on NV risk was assessed using a multiiterative bootstrap validation analysis. We identified strong interaction of genetics with AREDS formulation treatment on the development of NV. Individuals with high CFH and no ARMS2 risk alleles and taking the AREDS formulation had increased progression to NV compared with placebo. Those with low CFH risk and high ARMS2 risk had decreased progression risk. Analysis of CFH and ARMS2 genotype groups from a validation dataset reinforces this conclusion. Bootstrapping analysis confirms the presence of a genetics–treatment interaction and suggests that individual treatment response to the AREDS formulation is largely determined by genetics. The AREDS formulation modifies the risk of progression to NV based on individual genetics. Its use should be based on patient-specific genotype. National Academy of Sciences 2018-01-23 2018-01-08 /pmc/articles/PMC5789949/ /pubmed/29311295 http://dx.doi.org/10.1073/pnas.1718059115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Vavvas, Demetrios G.
Small, Kent W.
Awh, Carl C.
Zanke, Brent W.
Tibshirani, Robert J.
Kustra, Rafal
CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation
title CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation
title_full CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation
title_fullStr CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation
title_full_unstemmed CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation
title_short CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation
title_sort cfh and arms2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789949/
https://www.ncbi.nlm.nih.gov/pubmed/29311295
http://dx.doi.org/10.1073/pnas.1718059115
work_keys_str_mv AT vavvasdemetriosg cfhandarms2geneticriskdeterminesprogressiontoneovascularagerelatedmaculardegenerationafterantioxidantandzincsupplementation
AT smallkentw cfhandarms2geneticriskdeterminesprogressiontoneovascularagerelatedmaculardegenerationafterantioxidantandzincsupplementation
AT awhcarlc cfhandarms2geneticriskdeterminesprogressiontoneovascularagerelatedmaculardegenerationafterantioxidantandzincsupplementation
AT zankebrentw cfhandarms2geneticriskdeterminesprogressiontoneovascularagerelatedmaculardegenerationafterantioxidantandzincsupplementation
AT tibshiranirobertj cfhandarms2geneticriskdeterminesprogressiontoneovascularagerelatedmaculardegenerationafterantioxidantandzincsupplementation
AT kustrarafal cfhandarms2geneticriskdeterminesprogressiontoneovascularagerelatedmaculardegenerationafterantioxidantandzincsupplementation