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R. E. Hogg, A. E. Hughes, A. Muldrew, C. Patterson, U. Chakravarthy; Genotype-Phenotype Associations in Neovascular Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3442.
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To test the hypothesis that polymorphisms in CFH and LOC387715/HTRA1 may show differential associations with neovascular Age-related Macular Degeneration (AMD) clinical subtypes.
Polymorphisms in CFH and LOC387715/HTRA1 were genotyped in 392 participants, Categorization was based on the number of at-risk alleles (number of copies of CFH Haplotype-1 (GACG) or 2(GAAG) and of LOC387715/HTRA1 haplotype 2 (TA)) present for each participant. 226 had neovascular AMD and were recruited from a retinal clinic, the rest were obtained by community based sampling and consisted of 59 with soft drusen or pigmentary changes (early AMD) and 95 controls. Grading of fluorescein angiograms was undertaken to assign patients to one of two phenotypes; predominantly classic or predominantly occult based on the eye with more recent onset neovascular event. Multi-variate analysis was used to account for age, smoking status and history of cardiovascular disease. Those with early AMD were used as a reference category to dissect the genetic mechanisms driving RPE dysfunction from those driving the neovascular process.
Predominantly classic CNV was significantly associated with the number of CFH risk alleles present (p=0.011), LOC387715/HTRA1 haplotype 2 alleles present (p<0.001), smoking (ever vs never) (p=0.010), and history of cardiovascular disease (p=0.031). Presence of a predominantly occult lesion was associated with LOC387715/HTRA1 haplotype 2 alleles present (p<0.001) and history of cardiovascular disease (p=0.023).
Both systemic factors and genotype were found to influence the neovascular AMD lesion type.
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