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Genetic Factors in Age-Related Macular Degeneration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00058695
Recruitment Status : Terminated
First Posted : April 11, 2003
Last Update Posted : February 14, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )

Brief Summary:

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.


Condition or disease
Macular Degeneration

Detailed Description:

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 year 2020.7

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 treating AMD.

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Study Type : Observational
Actual Enrollment : 477 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Evaluation of Single Nucleotide Polymorphism (SNP) in Patients With and Subjects Without Age-Related Macular Degeneration (AMD)
Study Start Date : April 4, 2003
Study Completion Date : October 21, 2015

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Frequency of SNP [ Time Frame: Ongoing ]

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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 consent).

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 diseases.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00058695

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Eye Institute (NEI)
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Principal Investigator: Robert B Nussenblatt, M.D. National Eye Institute (NEI)

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Responsible Party: National Eye Institute (NEI) Identifier: NCT00058695     History of Changes
Other Study ID Numbers: 030155
First Posted: April 11, 2003    Key Record Dates
Last Update Posted: February 14, 2018
Last Verified: October 21, 2015
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) ):
Macualar Degeneration
Healthy Volunteer
Additional relevant MeSH terms:
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Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases