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Invest Ophthalmol Vis Sci. 2016 Nov 1;57(14):6107-6115. doi: 10.1167/iovs.16-19519.

Progression Rate From Intermediate to Advanced Age-Related Macular Degeneration Is Correlated With the Number of Risk Alleles at the CFH Locus.

Author information

1
John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States.
2
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States.
3
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States.
4
Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

Abstract

Purpose:

Progression rate of age-related macular degeneration (AMD) varies substantially, yet its association with genetic variation has not been widely examined.

Methods:

We tested whether progression rate from intermediate AMD to geographic atrophy (GA) or choroidal neovascularization (CNV) was correlated with genotype at seven single nucleotide polymorphisms (SNPs) in the four genes most strongly associated with risk of advanced AMD. Cox proportional hazards survival models examined the association between progression time and SNP genotype while adjusting for age and sex and accounting for variable follow-up time, right censored data, and repeated measures (left and right eyes).

Results:

Progression rate varied with the number of risk alleles at the CFH:rs10737680 but not the CFH:rs1061170 (Y402H) SNP; individuals with two risk alleles progressed faster than those with one allele (hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.08-2.40, P < 0.02, n = 547 eyes), although this was not significant after Bonferroni correction. This signal was likely driven by an association at the correlated protective variant, CFH:rs6677604, which tags the CFHR1-3 deletion; individuals with at least one protective allele progressed more slowly. Considering GA and CNV separately showed that the effect of CFH:rs10737680 was stronger for progression to CNV.

Conclusions:

Results support previous findings that AMD progression rate is influenced by CFH, and suggest that variants within CFH may have different effects on risk versus progression. However, since CFH:rs10737680 was not significant after Bonferroni correction and explained only a relatively small portion of variation in progression rate beyond that explained by age, we suggest that additional factors contribute to progression.

PMID:
27832277
PMCID:
PMC5104418
DOI:
10.1167/iovs.16-19519
[Indexed for MEDLINE]
Free PMC Article

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