Cargando…

Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration

PURPOSE: To investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD). METHODS: A total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy)...

Descripción completa

Detalles Bibliográficos
Autores principales: Woo, Se Joon, Ahn, Jeeyun, Morrison, Margaux A., Ahn, So Yeon, Lee, Jaebong, Kim, Ki Woong, DeAngelis, Margaret M., Park, Kyu Hyung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501798/
https://www.ncbi.nlm.nih.gov/pubmed/26171855
http://dx.doi.org/10.1371/journal.pone.0132771
_version_ 1782381123430514688
author Woo, Se Joon
Ahn, Jeeyun
Morrison, Margaux A.
Ahn, So Yeon
Lee, Jaebong
Kim, Ki Woong
DeAngelis, Margaret M.
Park, Kyu Hyung
author_facet Woo, Se Joon
Ahn, Jeeyun
Morrison, Margaux A.
Ahn, So Yeon
Lee, Jaebong
Kim, Ki Woong
DeAngelis, Margaret M.
Park, Kyu Hyung
author_sort Woo, Se Joon
collection PubMed
description PURPOSE: To investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD). METHODS: A total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy) and 154 typical choroidal neovascularization (CNV), and 395 control subjects without any evidence of AMD were enrolled. Full ophthalmologic examinations including fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were done, according to which patients were divided into either PCV or typical CNV. Standardized questionnaires were used to collect information regarding underlying systemic diseases, dietary habits, smoking history and body mass index (BMI). A total of 86 SNPs from 31 candidate genes were analyzed. Genotype association and logistic regression analyses were done and stepwise regression models to best predict disease for each AMD subtype were constructed. RESULTS: Age, spherical equivalent, myopia, and ever smoking were associated with exudative AMD. Age, hypertension, hyperlipidemia, spherical equivalent, and myopia were risk factors for typical CNV, while increased education and ever smoking were significantly associated with PCV (p<.05 for all). Four SNPs, ARMS2/HTRA1 rs10490924, rs11200638, and rs2736911, and CFH rs800292, showed association with exudative AMD. Two of these SNPs, ARMS2/HTRA1 rs10490924 and rs11200638, showed significant association with typical CNV and PCV specifically. There were no significant interactions between environmental and genetic factors. The most predictive disease model for exudative AMD included age, spherical equivalent, smoking, CFH rs800292, and ARMS2 rs10490924 while that for typical CNV included age, hyperlipidemia, spherical equivalent, and ARMS2 rs10490924. Smoking, spherical equivalent, and ARMS2 rs10490924 were the most predictive variables for PCV. When comparing PCV cases to CNV cases, age, BMI, and education were the most predictive risk factors of PCV. CONCLUSIONS: Only one locus, the ARMS2/HTRA1 was a significant genetic risk factor for Korean exudative AMD, including its subtypes, PCV and typical CNV. Stepwise regression revealed that CFH was important to risk of exudative AMD in general but not to any specific subtype. While increased education was a unique risk factor to PCV when compared to CNV, this association was independent of refractive error in this homogenous population from South Korea. No significant interactions between environmental and genetic risk factors were observed.
format Online
Article
Text
id pubmed-4501798
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-45017982015-07-17 Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration Woo, Se Joon Ahn, Jeeyun Morrison, Margaux A. Ahn, So Yeon Lee, Jaebong Kim, Ki Woong DeAngelis, Margaret M. Park, Kyu Hyung PLoS One Research Article PURPOSE: To investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD). METHODS: A total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy) and 154 typical choroidal neovascularization (CNV), and 395 control subjects without any evidence of AMD were enrolled. Full ophthalmologic examinations including fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were done, according to which patients were divided into either PCV or typical CNV. Standardized questionnaires were used to collect information regarding underlying systemic diseases, dietary habits, smoking history and body mass index (BMI). A total of 86 SNPs from 31 candidate genes were analyzed. Genotype association and logistic regression analyses were done and stepwise regression models to best predict disease for each AMD subtype were constructed. RESULTS: Age, spherical equivalent, myopia, and ever smoking were associated with exudative AMD. Age, hypertension, hyperlipidemia, spherical equivalent, and myopia were risk factors for typical CNV, while increased education and ever smoking were significantly associated with PCV (p<.05 for all). Four SNPs, ARMS2/HTRA1 rs10490924, rs11200638, and rs2736911, and CFH rs800292, showed association with exudative AMD. Two of these SNPs, ARMS2/HTRA1 rs10490924 and rs11200638, showed significant association with typical CNV and PCV specifically. There were no significant interactions between environmental and genetic factors. The most predictive disease model for exudative AMD included age, spherical equivalent, smoking, CFH rs800292, and ARMS2 rs10490924 while that for typical CNV included age, hyperlipidemia, spherical equivalent, and ARMS2 rs10490924. Smoking, spherical equivalent, and ARMS2 rs10490924 were the most predictive variables for PCV. When comparing PCV cases to CNV cases, age, BMI, and education were the most predictive risk factors of PCV. CONCLUSIONS: Only one locus, the ARMS2/HTRA1 was a significant genetic risk factor for Korean exudative AMD, including its subtypes, PCV and typical CNV. Stepwise regression revealed that CFH was important to risk of exudative AMD in general but not to any specific subtype. While increased education was a unique risk factor to PCV when compared to CNV, this association was independent of refractive error in this homogenous population from South Korea. No significant interactions between environmental and genetic risk factors were observed. Public Library of Science 2015-07-14 /pmc/articles/PMC4501798/ /pubmed/26171855 http://dx.doi.org/10.1371/journal.pone.0132771 Text en © 2015 Woo 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
Woo, Se Joon
Ahn, Jeeyun
Morrison, Margaux A.
Ahn, So Yeon
Lee, Jaebong
Kim, Ki Woong
DeAngelis, Margaret M.
Park, Kyu Hyung
Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration
title Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration
title_full Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration
title_fullStr Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration
title_full_unstemmed Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration
title_short Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration
title_sort analysis of genetic and environmental risk factors and their interactions in korean patients with age-related macular degeneration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501798/
https://www.ncbi.nlm.nih.gov/pubmed/26171855
http://dx.doi.org/10.1371/journal.pone.0132771
work_keys_str_mv AT woosejoon analysisofgeneticandenvironmentalriskfactorsandtheirinteractionsinkoreanpatientswithagerelatedmaculardegeneration
AT ahnjeeyun analysisofgeneticandenvironmentalriskfactorsandtheirinteractionsinkoreanpatientswithagerelatedmaculardegeneration
AT morrisonmargauxa analysisofgeneticandenvironmentalriskfactorsandtheirinteractionsinkoreanpatientswithagerelatedmaculardegeneration
AT ahnsoyeon analysisofgeneticandenvironmentalriskfactorsandtheirinteractionsinkoreanpatientswithagerelatedmaculardegeneration
AT leejaebong analysisofgeneticandenvironmentalriskfactorsandtheirinteractionsinkoreanpatientswithagerelatedmaculardegeneration
AT kimkiwoong analysisofgeneticandenvironmentalriskfactorsandtheirinteractionsinkoreanpatientswithagerelatedmaculardegeneration
AT deangelismargaretm analysisofgeneticandenvironmentalriskfactorsandtheirinteractionsinkoreanpatientswithagerelatedmaculardegeneration
AT parkkyuhyung analysisofgeneticandenvironmentalriskfactorsandtheirinteractionsinkoreanpatientswithagerelatedmaculardegeneration