Role of complement factor H I62V and age-related maculopathy susceptibility 2 A69S variants in the clinical expression of polypoidal choroidal vasculopathy
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Published on: July 14, 2016
Yoichi Sakurada1, Takeo Kubota, Mitsuhiro Imasawa
1Department of Ophthalmology, University of Yamanashi, Yamanashi, Japan. sakurada@yamanashi.ac.jp
Insights
Genetic variants in age-related maculopathy susceptibility 2 (ARMS2) A69S are linked to polypoidal choroidal vasculopathy (PCV) clinical features, including hemorrhagic lesions and earlier onset. Complement factor H (CFH) I62V showed no association.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Polypoidal choroidal vasculopathy (PCV) is a subtype of age-related macular degeneration.
- Genetic factors, including variants in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2), are implicated in AMD pathogenesis.
- The specific role of these variants in PCV clinical characteristics requires further investigation.
Purpose of the Study:
- To investigate the association between CFH I62V (rs800292) and ARMS2 A69S (rs10490924) genetic variants and the clinical presentation of PCV.
- To determine if these variants influence specific funduscopic findings, disease bilaterality, or age of onset in PCV patients.
Main Methods:
- A cross-sectional study involving 226 Japanese patients with PCV.
- Genotyping for CFH I62V and ARMS2 A69S variants using TaqMan and denaturing high-performance chromatography, respectively.
- Analysis of the association between genotypes and five funduscopic findings: serous retinal detachment, subretinal hemorrhage, serous pigment epithelial detachment (PED), hemorrhagic PED, and classic choroidal neovascularization (CNV), as well as disease bilaterality and age at onset.
Main Results:
- ARMS2 A69S at-risk variants were significantly associated with increased incidence of subretinal hemorrhage, serous PED, and hemorrhagic PED.
- ARMS2 A69S homozygosity showed a 12.4-fold increased likelihood of hemorrhagic PED and was associated with earlier PCV onset (mean age 68.8 years) and higher frequency in bilateral cases.
- CFH I62V variants and classic CNV showed no significant association with any PCV phenotypes studied; ARMS2 A69S was linked to a lower incidence of serous retinal detachment.
Conclusions:
- ARMS2 A69S variants are significantly associated with specific clinical manifestations in PCV, particularly hemorrhagic or sub-RPE lesions, earlier disease onset, and bilateral involvement.
- Genotyping of ARMS2 A69S provides more clinical insight into PCV than CFH I62V genotyping.
- These findings highlight the importance of ARMS2 A69S in understanding PCV pathogenesis and clinical heterogeneity.
Purpose:
To investigate the role of complement factor H (CFH) I62V (rs800292) and age-related maculopathy susceptibility 2 (ARMS2) A69S (rs10490924) variants in the clinical characteristics of polypoidal choroidal vasculopathy (PCV).
Design:
Cross-sectional study.
Participants:
A total of 226 Japanese patients with PCV in both eyes (44 cases) or in 1 eye (182 cases).
Methods:
Genotyping was performed in all cases for CFH I62V using TaqMan technology and for ARMS2 A69S by denaturing high-performance chromatography. The incidence of 5 characteristic funduscopic findings was studied, including serous retinal detachment, subretinal hemorrhage, serous pigment epithelial detachment (PED), hemorrhagic PED, and classic choroidal neovascularization (CNV).
Main Outcome Measures:
The association of clinical phenotypes, including the incidence of each of 5 specific fundus findings, bilaterality of the disease, and age at onset, with variants of CFH I62V or ARMS2 A69S.
Results:
Although there was no association of CFH I62V variants with any of the phenotypes in PCV, at-risk variants of ARMS2 A69S were associated with higher incidences of subretinal hemorrhage, serous PED, and hemorrhagic PED. In particular, the at-risk allele homozygosity of ARMS2 A69S increased the likelihood for hemorrhagic PED by 12.4-fold compared with non-carriers of the allele (confidence interval, 1.60-95.1, P = 0.0001). However, the at-risk allele of ARMS2 A69S was associated with a lower incidence of serous retinal detachment (P = 0.0092). Classic CNV was not associated with either variant. The mean age at the onset of PCV was significantly younger (68.8 years) in those with homozygosity of the at-risk allele of ARMS2 A69S than in those with heterozygosity (71.6 years) or in non-carriers (72.6 years) (P = 0.026). Moreover, the at-risk allele frequencies of the ARMS2 A69S were significantly higher in bilateral cases than in unilateral cases (75.0% vs. 59.3%, P = 0.007).
Conclusions:
ARMS2 A69S variants were significantly associated with hemorrhagic or subpigment epithelium lesions of PCV, and with earlier onset and bilateral involvement. The genotyping of ARMS2 A69S is more informative than that of CFH I62V in understanding the clinical features in patients with PCV.
