This study will examine whether certain polymorphisms (small gene variances) predispose
people to develop age-related macular degeneration (AMD). This eye condition affects people
over 50 years of age and can cause permanent loss of central vision. The study will examine
and compare the frequency of polymorphisms in patients with AMD to that of individuals
without AMD. This information will help identify genetic risk factors for the AMD and may
lead to the development of more effective treatments.
Patients 50 years of age and older with advanced AMD and healthy normal volunteers may be
eligible for this study. All participants will provide an eye health history and will have 10
milliliters (2 teaspoons) of blood drawn from an arm vein. The DNA in the blood will be
isolated and tested for certain genes that other research indicates are important in aging
and age-related diseases. The normal and polymorphic gene sequences will be identified and
compared in patients with AMD and control subjects to determine if any of the polymorphisms
are related to development of AMD.
In addition, control subjects will have a routine eye examination, including dilation of the
pupils for examination of the back of the eye.
Age-related macular degeneration (AMD) is the leading cause of irreversible severe central
visual loss older than 50 in the world.1 The incidence and progression of all the features of
AMD are known to increase significantly with age.2-4 In a recent study, Klein et al. reported
that approximately 15.6% of the US population aged 60 years and older in 2005-2008 had signs
of AMD.5 In a study in Iceland, the prevalence of early AMD was 12.4% for those aged 66 to 74
years and 36% for those aged 85 years and older.6 Currently in the United States, advanced
AMD affects more than 1.75 million people and the number will increase to 2.95 million by the
Epidemiological studies of genome wide association study (GWAS), candidate gene association,
and linkage disequilibrium suggest that AMD has a significant genetic component.7-10 Ample
evidence supports the hypothesis that variance of genes involved in DNA repair,11-13
oxidative stress14, 15 and inflammation16-20 play a role in aging and age-related diseases.
Many studies have documented the association between polymorphisms in complement factors
(CF), oxidative stress, apolipoprotein E (ApoE), mitochondria and chaperone proteins genes
and AMD.21-23 Single nucleotide polymorphism (SNP) in ApoE, ApoE or C2/BF may protect AMD. On
the other hand, SNP in CFH, AMRS2/HTRA-1 or CX3CR1 gene may increase AMD risk.24 In this
study, we would like to test whether the variations of biologically plausible genes (or the
modifying genes) listed above are differentially distributed in AMD patients and normal
populations. To this end, we choose genes that are believed to play a crucial role in the
aging process and will analyze the frequency of SNPs specifically within the coding frames of
biologically plausible genes responsible for aging and age-related diseases.
Our aim will be to compare the allelic frequencies of candidate genes listed above in cohorts
with AMD to the frequency in normal control subjects without AMD. With this study we hope to
identify genetic risk factors that could have functional implications for understanding and
- INCLUSION CRITERIA:
AMD Patients (cases):
1. Diagnosis of advanced AMD defined by geographic atrophy and/or choroidal
neovascularization with drusen of any size in at least one eye.
2. Age 50 years or older.
3. If sample previously donated in a different study, the patient has given their
permission to use their sample (i.e. marked appropriate selection in the informed
Control Patients (controls):
1. Absence of drusen or no more than 5 drusen less than 63 microns, absence of other
diagnostic criteria for AMD.
2. Agrees to undergo study examinations.
1. Presence of retinal disease involving the photoreceptors and/or outer retinal layers
other than AMD loss such as high myopia, retinal dystrophies, central serous
retinopathy, vein occlusion, diabetic retinopathy and uveitis or similar outer retinal
diseases that have been present prior to the age of 50.
2. Opacities of the ocular media, limitations of papillary dilation or other problems
sufficient to preclude adequate stereo fundus photography. These conditions include
occluded pupils due to synechiae, cataracts, vitreous haze and opacities due to ocular