Genetic factors for choroidal neovascularization associated with high myopia

Nicolas Leveziel; Yi Yu; Robyn Reynolds; Albert Tai; Weihua Meng; Violaine Caillaux; Patrick Calvas; Bernard Rosner; Francois Malecaze; Eric H. Souied; Johanna M. Seddon

doi:10.1167/iovs.12-9538

Genetic factors for choroidal neovascularization associated with high myopia

Nicolas Leveziel, Yi Yu, Robyn Reynolds, Albert Tai, Weihua Meng, Violaine Caillaux, Patrick Calvas, Bernard Rosner, Francois Malecaze, Eric H. Souied, Johanna M. Seddon

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Abstract

PURPOSE. Nonsyndromic high myopia, defined by a refractive error greater than -6 diopters (D), is associated with an increased risk of macular choroidal neovascularization (CNV), a vision-threatening complication. The aim of this study was to investigate whether genetic factors associated with age-related macular degeneration (AMD) are related to myopic CNV.

METHODS. We conducted a case-control study, including 71 cases with myopic CNV and 196 myopic controls without CNV, from Creteil and Toulouse, France, and Boston, MA. Single nucleotide polymorphisms (SNPs) from 15 genes reported to be related to AMD were selected for association testing in this study.

RESULTS. In univariate analysis, the rs10033900 SNP located in CFI was associated with myopic CNV (P = 0.0011), and a SNP in APOE was also related (P = 0.041). After adjustment for age, sex, and degree of myopia, SNPs in three genes were significantly associated, including CFI (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.37, P = 0.0023), COL8A1 (OR 1.88, 95% CI 1.18-2.98, P = 0.0076), and CFH (OR 1.65, 95% CI 1.02-2.66, P = 0.04). After correction for multiple testing, only CFI remained significantly related to high myopic CNV (P = 0.045).

CONCLUSIONS. We report the first genetic associations with choroidal neovascularization (CNV) in a high myopic Caucasian population. One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic CNV in multivariate analysis after correction for multiple testing. This SNP is a plausible biological marker associated with CNV outgrowth among highmyopic patients. Results generate hypotheses about potential loci related to CNV in high myopia, and larger studies are needed to expand on these findings. (Invest Ophthalmol Vis Sci. 2012;53:5004-5009) DOI:10.1167/iovs.12-9538

Original language	English
Pages (from-to)	5004-5009
Number of pages	6
Journal	Investigative Ophthalmology & Visual Science
Volume	53
Issue number	8
DOIs	https://doi.org/10.1167/iovs.12-9538
Publication status	Published - Jul 2012
Event	Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology - Ft Lauderdale Duration: 9 May 2012 → …

Keywords

MACULAR DEGENERATION
ELDERLY JAPANESE POPULATION
APOLIPOPROTEIN-E GENE
GENOME-WIDE ASSOCIATION
LINKAGE ANALYSIS
HIGH-GRADE MYOPIA
PATHOLOGICAL MYOPIA
DOMINANT HIGH MYOPIA
CHINESE FAMILY
SUSCEPTIBILITY LOCUS

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@article{d80f5230616249288215bd884c7c301e,

title = "Genetic factors for choroidal neovascularization associated with high myopia",

abstract = "PURPOSE. Nonsyndromic high myopia, defined by a refractive error greater than -6 diopters (D), is associated with an increased risk of macular choroidal neovascularization (CNV), a vision-threatening complication. The aim of this study was to investigate whether genetic factors associated with age-related macular degeneration (AMD) are related to myopic CNV.METHODS. We conducted a case-control study, including 71 cases with myopic CNV and 196 myopic controls without CNV, from Creteil and Toulouse, France, and Boston, MA. Single nucleotide polymorphisms (SNPs) from 15 genes reported to be related to AMD were selected for association testing in this study.RESULTS. In univariate analysis, the rs10033900 SNP located in CFI was associated with myopic CNV (P = 0.0011), and a SNP in APOE was also related (P = 0.041). After adjustment for age, sex, and degree of myopia, SNPs in three genes were significantly associated, including CFI (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.37, P = 0.0023), COL8A1 (OR 1.88, 95% CI 1.18-2.98, P = 0.0076), and CFH (OR 1.65, 95% CI 1.02-2.66, P = 0.04). After correction for multiple testing, only CFI remained significantly related to high myopic CNV (P = 0.045).CONCLUSIONS. We report the first genetic associations with choroidal neovascularization (CNV) in a high myopic Caucasian population. One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic CNV in multivariate analysis after correction for multiple testing. This SNP is a plausible biological marker associated with CNV outgrowth among highmyopic patients. Results generate hypotheses about potential loci related to CNV in high myopia, and larger studies are needed to expand on these findings. (Invest Ophthalmol Vis Sci. 2012;53:5004-5009) DOI:10.1167/iovs.12-9538",

keywords = "MACULAR DEGENERATION, ELDERLY JAPANESE POPULATION, APOLIPOPROTEIN-E GENE, GENOME-WIDE ASSOCIATION, LINKAGE ANALYSIS, HIGH-GRADE MYOPIA, PATHOLOGICAL MYOPIA, DOMINANT HIGH MYOPIA, CHINESE FAMILY, SUSCEPTIBILITY LOCUS",

author = "Nicolas Leveziel and Yi Yu and Robyn Reynolds and Albert Tai and Weihua Meng and Violaine Caillaux and Patrick Calvas and Bernard Rosner and Francois Malecaze and Souied, {Eric H.} and Seddon, {Johanna M.}",

year = "2012",

month = jul,

doi = "10.1167/iovs.12-9538",

language = "English",

volume = "53",

pages = "5004--5009",

journal = "Investigative Ophthalmology & Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology Inc.",

number = "8",

note = "Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology ; Conference date: 09-05-2012",

}

TY - JOUR

T1 - Genetic factors for choroidal neovascularization associated with high myopia

AU - Leveziel, Nicolas

AU - Yu, Yi

AU - Reynolds, Robyn

AU - Tai, Albert

AU - Meng, Weihua

AU - Caillaux, Violaine

AU - Calvas, Patrick

AU - Rosner, Bernard

AU - Malecaze, Francois

AU - Souied, Eric H.

AU - Seddon, Johanna M.

PY - 2012/7

Y1 - 2012/7

N2 - PURPOSE. Nonsyndromic high myopia, defined by a refractive error greater than -6 diopters (D), is associated with an increased risk of macular choroidal neovascularization (CNV), a vision-threatening complication. The aim of this study was to investigate whether genetic factors associated with age-related macular degeneration (AMD) are related to myopic CNV.METHODS. We conducted a case-control study, including 71 cases with myopic CNV and 196 myopic controls without CNV, from Creteil and Toulouse, France, and Boston, MA. Single nucleotide polymorphisms (SNPs) from 15 genes reported to be related to AMD were selected for association testing in this study.RESULTS. In univariate analysis, the rs10033900 SNP located in CFI was associated with myopic CNV (P = 0.0011), and a SNP in APOE was also related (P = 0.041). After adjustment for age, sex, and degree of myopia, SNPs in three genes were significantly associated, including CFI (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.37, P = 0.0023), COL8A1 (OR 1.88, 95% CI 1.18-2.98, P = 0.0076), and CFH (OR 1.65, 95% CI 1.02-2.66, P = 0.04). After correction for multiple testing, only CFI remained significantly related to high myopic CNV (P = 0.045).CONCLUSIONS. We report the first genetic associations with choroidal neovascularization (CNV) in a high myopic Caucasian population. One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic CNV in multivariate analysis after correction for multiple testing. This SNP is a plausible biological marker associated with CNV outgrowth among highmyopic patients. Results generate hypotheses about potential loci related to CNV in high myopia, and larger studies are needed to expand on these findings. (Invest Ophthalmol Vis Sci. 2012;53:5004-5009) DOI:10.1167/iovs.12-9538

AB - PURPOSE. Nonsyndromic high myopia, defined by a refractive error greater than -6 diopters (D), is associated with an increased risk of macular choroidal neovascularization (CNV), a vision-threatening complication. The aim of this study was to investigate whether genetic factors associated with age-related macular degeneration (AMD) are related to myopic CNV.METHODS. We conducted a case-control study, including 71 cases with myopic CNV and 196 myopic controls without CNV, from Creteil and Toulouse, France, and Boston, MA. Single nucleotide polymorphisms (SNPs) from 15 genes reported to be related to AMD were selected for association testing in this study.RESULTS. In univariate analysis, the rs10033900 SNP located in CFI was associated with myopic CNV (P = 0.0011), and a SNP in APOE was also related (P = 0.041). After adjustment for age, sex, and degree of myopia, SNPs in three genes were significantly associated, including CFI (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.37, P = 0.0023), COL8A1 (OR 1.88, 95% CI 1.18-2.98, P = 0.0076), and CFH (OR 1.65, 95% CI 1.02-2.66, P = 0.04). After correction for multiple testing, only CFI remained significantly related to high myopic CNV (P = 0.045).CONCLUSIONS. We report the first genetic associations with choroidal neovascularization (CNV) in a high myopic Caucasian population. One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic CNV in multivariate analysis after correction for multiple testing. This SNP is a plausible biological marker associated with CNV outgrowth among highmyopic patients. Results generate hypotheses about potential loci related to CNV in high myopia, and larger studies are needed to expand on these findings. (Invest Ophthalmol Vis Sci. 2012;53:5004-5009) DOI:10.1167/iovs.12-9538

KW - MACULAR DEGENERATION

KW - ELDERLY JAPANESE POPULATION

KW - APOLIPOPROTEIN-E GENE

KW - GENOME-WIDE ASSOCIATION

KW - LINKAGE ANALYSIS

KW - HIGH-GRADE MYOPIA

KW - PATHOLOGICAL MYOPIA

KW - DOMINANT HIGH MYOPIA

KW - CHINESE FAMILY

KW - SUSCEPTIBILITY LOCUS

U2 - 10.1167/iovs.12-9538

DO - 10.1167/iovs.12-9538

M3 - Article

C2 - 22678500

SN - 0146-0404

VL - 53

SP - 5004

EP - 5009

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 8

T2 - Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology

Y2 - 9 May 2012

ER -

Genetic factors for choroidal neovascularization associated with high myopia

Abstract

Keywords

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