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Daniela Ferrara, Johanna M Seddon; Phenotypic Characterization of Complement Factor H R1210C Rare Genetic Variant in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):785.
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The complement factor H (CFH) gene R1210C rare variant confers the strongest genetic risk factor for age-related macular degeneration (AMD), but its associated phenotype has not been well characterized. We performed a retrospective, observational study to investigate specific fundus features of a Caucasian population with the R1210C rare variant.
Enrolled subjects with the variant and their family members without the variant were identified from the AMD Registry for a family based study arm. For subjects with the variant but without a family member enrolled in the study, age-matched controls without the variant were randomly selected from the Registry. Fundus features specific for diagnosis and disease staging were retrospectively characterized by systematic review of all fundus images for each subject, including color photography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography. Presence of drusen in the macula (macular drusen score) and estimated number (total macular drusen score) were assessed. Presence of drusen in the extramacular regions (extramacular drusen score), pigmentary changes, and disease staging were also evaluated. Binary logistic regression models were used to evaluate the association between rare variant status and ocular phenotypes.
A total of 143 subjects (283 eyes), including 62 subjects with the rare variant were included. Drusen score covariates were significantly associated with the R1210C rare variant. A larger proportion of subjects carrying the variant compared to those without the variant had high levels of all drusen scores (P<0.001 for each score). Subjects carrying the rare variant had a much greater likelihood of having advanced disease (odds ratio: 7.0, 95% confidence interval: 3.1-16.2, P<0.001). The higher prevalence of geographic atrophy among subjects carrying the variant was particularly noteworthy (OR: 13.7, p<0.001).
The typical phenotype of CFH R1210C rare variant is significantly associated with extensive drusen accumulation in the macula and throughout the fundus, as well as with high risk of having advanced disease, especially geographic atrophy. Better characterization of genetic profiles in AMD will be important for screening and future therapeutic strategies for this vision-threatening condition.
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