Purchase this article with an account.
R.J. Ross, C.M. Bojanowski, E.Y. Chew, F.L. Ferris, III, C.–C. Chan, J. Tuo; Association Between LOC387715 and Age–Related Macular Degeneration, a Replication Study With AREDS Samples . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5820.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Several studies have provided evidence that genetic variation plays an important role in the development and pathogenesis of age–related macular degeneration (AMD). Allelic variation within complement factor H (CFH) has been identified as an important risk factor for AMD development. In a recent meta–analysis, chromosome 10q26 was reported as the strongest AMD linked locus. LOC387715, located on chromosome 10q26, was recently reported as another susceptibility gene for AMD in two independent studies. The present study further investigates the association between LOC387715, CFH, and AMD using an Age–Related Eye Disease Study (AREDS) cohort.
A cohort of 459 advanced AMD cases (geographic atrophy involving the macula and/or choroidal neovascularization with drusen in at least one eye) and 285 age–matched controls was included. The control subjects were clinically evaluated and showed an absence of drusen or less than 5 small drusen (<63µm), no evidence of significant extra–macular drusen, and an absence of all other retinal disease affecting the photoreceptors and/or outer retinal layers. LOC387715 (rs10490924, Ala69Ser) and CFH intron G/C (rs380390) SNPs were genotyped using PCR–RFLP. Chi–square testing was performed for case–control analysis. Logistic regression was used for interaction analysis.
Prevalence of the LOC387715 Ala69Ser SNP was significantly increased in the AMD cases as compared to the controls (38.2% vs.19.79%, P < 0.0001) with an Odds Ratio (OR) of 7.23. A significantly increased prevalence of the CFH intron G/C SNP was also found in cases relative to controls (61.1% vs. 38.4%); odds ratios were 5.51 (C/C vs. G/G) and 1.75 (G/C vs. G/G). An additive model was observed indicating a strong synergic effect of LOC387715 Ala69Ser and CFH intron G/C SNPs with a combined OR of 23.43.
Replication of the reported association in the AREDS samples strongly suggests that LOC387715 is a true susceptibility gene for AMD. Individuals carrying both of the CFH and LOC387715 risk alleles are highly predisposed to AMD development. LOC387715 serves as a potentially significant candidate gene for future AMD functional studies.
This PDF is available to Subscribers Only