Genetic analysis of simultaneous geographic atrophy and choroidal neovascularization.
OBJECTIVE
To investigate clinical presentation and genotypes in patients with simultaneous geographic atrophy (GA) and choroidal neovascularization (CNV) and to compare with patients with GA or CNV only.


METHODS
Twenty patients with combined CNV-GA and 154 CNV only and 154 GA only were chosen based on clinical exam and imaging. Six single-nucleotide polymorphisms (SNPs)-rs2274700 and rs1061170 (complement factor H), rs10490924 and rs11200638 (HTRA1/LOC387715), rs2230199 (C3), rs9332739 (C2)-were genotyped using the SNaPshot method. Chi-squared tests were used for genetic analysis.


RESULTS
In patients with CNV-GA, GA progressed slowly and often preceded CNV. CNV presented as subretinal haemorrhage or fluid, with a sudden drop in visual acuity (VA). Comparing combined CNV-GA to GA and CNV only, patients with both had a higher frequency of at-risk alleles at both SNPs within the HTRA1 gene-rs10490924 (52.5%), rs11200638 (52.6%). Statistical significance was not achieved. CNV-GA patients had no protective alleles at SNP rs9332739 (C2), compared with GA (27%) and CNV only (10%).


CONCLUSIONS
There is a paucity of reports describing simultaneous CNV-GA. Clinical and genetic results may support the fact that GA and CNV fit on an age-related macular degeneration (AMD)-disease continuum and may clarify the disease processes in AMD.
Department of Ophthalmology and Shiley Eye Center, and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
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S
Grob
J
J
Luo
G
G
Hughes
C
C
Lee
X
X
Zhou
J
J
Lee
H
H
Du
H
H
Ferreyra
W R
WR
Freeman
I
I
Kozak
K
K
Zhang
D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000235:genetics* / Q000503:physiopathology; D003175:Complement C2 / Q000235:genetics*; D003176:Complement C3 / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005451:Fluorescein Angiography; D005787:Gene Frequency; D005838:Genotype; D057092:Geographic Atrophy / Q000235:genetics* / Q000503:physiopathology; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012697:Serine Endopeptidases / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
C493495:CFH protein, human; D003175:Complement C2; D003176:Complement C3; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases