Personalized Cardiology - Applications of Biotechnology in Cardiovascular Therapeutics - page 318

a potentially fatal cardiac disorder associated with serious arrhythmias. Some of the
genes that cause cardiovascular diseases are shown in Table 10.1 .
Long Q-T syndrome is an inherited form of ventricular arrhythmia in which the
interval between the Q and the T waves is longer than normal. This disease reflects
a defect in the electrical properties of the cardiac muscle, which predisposes the
patient to life-threatening ventricular fibrillation after stress. Five genes have been
identified where the mutations are associated with this disorder. These genes
encode cardiac potassium ion channels and support the hypothesis that the LQT
syndrome results from delayed myocellular repolarization. The diagnosis of long
QT syndrome and other channelopathies by an electrocardiogram is often difficult
and may be missed, which leaves a patient at risk for sudden cardiac death.
FAMILION™ (originally from Genaissance now taken over by Cogenics) is the
first commercially available, comprehensive genetic test for a heart rhythm disorder.
This DNA test for cardiac ion channel mutations may remove uncertainty for the
patients, their families, and their physicians with respect to establishing a diagnosis
and can guide the physician in determining the best treatment options for those
who are genetically predisposed to potentially fatal cardiac arrhythmias caused by
long QT syndrome and related cardiac ion channel diseases. The test examines five
cardiac ion channel genes for a mutation that is likely to cause long QT syndrome.
If a genetic mutation is detected, its type and location can assist the physician in
making treatment selections that could include lifestyle modification, prescription
or avoidance of specific classes of drugs or the implantation of a defibrillator. A
patient's family members also benefit from the test because it can identify if they
inherited the same mutation as the initially symptomatic patient and may be at risk
of a potentially fatal arrhythmia. These relatives often have ambiguous findings on
an ECG, while the results of the FAMILION Test can answer whether or not they
carry the familial mutation.
Gene Variant as a Risk Factor for Sudden Cardiac Death
Extremes of the electrocardiographic QT interval, a measure of cardiac repolariza-
tion, are associated with increased cardiovascular mortality. A gene called NOS1AP
(CAPON), which may predispose some people to abnormal heart rhythms leading
to sudden cardiac death, was identified through a genome-wide association study
(Arking et al. 2006 ). Statistically significant findings were validated in two indepen-
dent samples of 2,646 subjects from Germany and 1,805 subjects from the USA
Framingham Heart Study. NOS1AP, a regulator of neuronal nitric oxide synthase
(nNOS), modulates cardiac repolarization. The gene, not previously discovered by
traditional gene-hunting approaches, appears to influence significantly QT interval
length as risk factor for sudden cardiac death. QT interval can be measured
noninvasively with an EKG, and each person's QT interval, in the absence of a major
cardiovascular event, is stable over time, making it a reliable measure. Approximately,