Age-Related Macular Degeneration, Risk Analysis, Y402H & A69S, Blood

CPT CODE:

USEFUL FOR:

Risk assessment, diagnosis, and clinical management of age-relatedmacular degeneration (ARMD), when interpreted in conjunction withother ARMD risk factors and clinical presentation

SPECIMEN REQUIRED:

"Molecular Genetics - Congenital Inherited DiseasesPatient Information Sheet" (Supply T521 or see SpecialInstructions) is required for all orders. If not orderingelectronically, please submit the above information sheet alongwith a "Molecular Genetics Request Form" (Supply T245) with thespecimen. An "Informed Consent for DNA Testing"(Supply T576)is available. See Special Instructions for a copy of the form.
Specimen must arrive within 96 hours of draw.
Draw blood in a lavender-top (EDTA) tube or a yellow-top (ACD) tube, and send 3 mL of EDTA or ACD whole blood in original VACUTAINER. Invert several times to mix blood.Forward unprocessed whole blood promptly at ambienttemperature.

TRANSPORT TEMPERATURE:

Ambient\Refrig OK\Frozen NO

CLINICAL INFORMATION:

Age-related macular degeneration (ARMD) is recognized as a leadingcause of blindness in the United States and other developed countries.Patients with ARMD typically show photoreceptor dysfunction and,ultimately, central vision loss sometime after the age of 50. While somepatients are entirely asymptomatic, typical symptoms include blurred ordistorted vision. Difficulty adjusting to dim light is another common symptom. Onset of symptoms is typically gradual, however, in rare cases, rapid progression is observed.
There are 2 general types of ARMD, classified as "dry" and "wet."Dry macular degeneration is more common (90% of cases), andshows more gradual visual changes that correlate with the loss offunction in corresponding areas of the retina. With this form of maculardegeneration, the transport of nutrients and wastes across the retinalpigment epithelium (RPE) slows, causing damage to photoreceptors. Accumulations of waste products under the RPE form drusen, a clinical hallmark of ARMD. Typically, when observed in the context of ARMD, drusen are characterized as "soft" or "indistinct" deposits measuring > or =63 micrometers. Wet macular degeneration accounts forapproximately 10% of cases and shows a more rapid progression andsevere disease. Choroidal neovascularization (CNV) occurs in responseto the decreased supply of nutrients and slow transport of wastes.These newly formed blood vessels are delicate and leak blood or fluidunder the retina causing the retinal surface to become uneven. As aresult, vision may be distorted.
The lifetime risk for ARMD in Caucasians is estimated to be 1/10. (1) ARMD, both wet and dry types, is considered a multifactorial disorder, as it is thought to develop due to interplay between environmental and genetic risk and protective factors. Someof these factors are modifiable, others are not. Modifiable risk factorsinclude cigarette smoking (smokers show a 2-fold higher risk ofdeveloping disease), exposure to second-hand cigarette smoke, sunexposure, and dietary antioxidants (possibly protective against ARMD).Nonmodifiable risk factors include gender (females show a 2-fold higherrisk of developing the disease), ethnic background (African Americansshow half the risk of Caucasian individuals), age, and genotype. Whilethere is no single gene attributed to ARMD, genetic variants (risk factors)have been identified.
At least 2 genetic variants (Y402H and A69S) have been found to be associated with an increased risk for A

CLINICAL INTERPRETATION:

An interpretive report including an overview of the results and their significance is provided.
It is important to interpret molecular genetic results within the context of the aforementioned risk and protective factors. Certainly, the risk factor genotype may provide useful clinical information. However, data to date does not suggest that genotype information can be used in isolation to determine a diagnosis of ARMD. Patient-specific risks generated from combining clinical (environmental) information and genotype information are not available. Currently, we cannot accurately quantify the collective influence of known and unknown, modifiable and not modifiable risk factors to provide a combined risk assessment for individual patients. However, genotype information can be clinically useful when making medical management decisions (investigation for inflammatory markers in individuals with the Y402H risk factor [2],) and emphasizing to patients the benefits of smoking cessation (Schmidt et al, suggests the importance of this, particularly in individuals with the A69S risk factor), dietary modification, etc. (3) In some cases, genotype information may also assist with clinical diagnosis.

REFERENCE VALUES:

An interpretive report will be provided.