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G. J. McKay, G. Silvestri, N. Orr, U. Chakravarthy, A. E. Hughes; Genetic Interaction Assessment of Age Related Macular Degeneration (AMD) Susceptibility Loci Within the Northern Ireland Population. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4630.
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To assess: 1) the genetic interaction between Complement factor H, Factor B and Complement component C2 and the independent influence of Vascular Endothelial Growth Factor within an AMD cohort from Northern Ireland.
Venous blood samples (6ml) were collected from patient samples (n=250) with documented end-stage wet AMD and an age and sex-matched control cohort (n=250). All patients underwent full ophthalmic examination and participated in a short questionnaire to detail history of smoking, micro and macro angiopathic disease, drug history, refractive status, eye colour, body mass index and family history. Genetic haplotype analysis was undertaken for Complement Factor H (CFH), CFHR1, CFHR3, LOC387715, Complement Factor B (FB), Complement component 2 (C2) and Vascular Endothelial Growth Factor (VEGF). Haplotypic structure was determined using information derived from the HapMap project for each of the seven genes including predicted promoter regions. Thirty SNPs were determined to provide sufficient information to elucidate the haplotypic structure for each gene and these were multiplexed in 4 reactions using the SNaPshot technology platform (ABI).
Preliminary data analysis suggests a high incidence of AMD risk haplotypes within the affected cohort with a decreasing incidence of protective haplotypes when compared to the control cohort. Comparisons between the incidence of these haplotypes within each cohort is being further investigated to ascertain which genes are most likely to be most significantly associated with AMD within this population. Genetic variation within C2 and FB would appear to be less strongly associated with the disease cohort than previously reported by other studies. Interestingly, preliminary analysis does not suggest a significant role for VEGF in relation to wet AMD with these patient samples.
Our results show that this simple multiplex analysis can quickly determine the haplotypic structure across a number of disease loci previously associated with AMD. Sample size might potentially prove to be important in the determination of the significance attributed to the various alleles in relation to AMD. It would appear that CFH and LOC387715 remain by far, the most likely genetic factors to be associated with AMD within this patient cohort and that VEGF is unlikely to have any significant involvement with the disease manifestation within this population.
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