485Instead of focusing on so-called candidate genes with known functions that are
highly suspect in heart beat rhythm, the researchers fi rst focused on people who
have extremely long or short QT intervals. They used subjects from two population-
based studies, about 1,800 American adults of European ancestry from the
Framingham Heart Study of Framingham, Massachusetts, and about 6,700 German
adults from the KORA-gen study of Augsburg, Germany. They looked at SNPs that
track with having a long or short QT interval. Only one particular SNP correlated
with QT interval. That SNP was found near the NOS1AP gene, which has been
studied for its function in nerve cells and was not previously suspected to play a role
in heart function.
Identifying those at high risk for sudden cardiac death before fatalities occur has
been challenging, both at the clinical and at the genetic level. In more than one third
of all cases, sudden cardiac death is the fi rst hint of heart disease. It is widely
believed that many factors, genetic and environmental, contribute to irregular heart-
beat and other conditions that may lead to sudden cardiac death. Now that variants
of the NOS1AP gene have been correlated with QT interval length, the next project
would be to fi gure out exactly how the DNA sequence variations alter the function
of the gene, and how changes in gene function affects heart rhythm. Being able to
identify predisposed individuals can save their lives by prescribing beta-blockers
and other drugs that regulate heart rhythm, and even by implanting automatic defi -
brillators in those with the highest risk.
KIF6 Gene Test as a Guide to Management of Heart Disease
Carriers of the KIF6 (kinesin family member 6) wild-type gene are 50–55 % more
likely to develop coronary heart disease (CHD). KIF6 as a biomarker of CHD is the
basis of a genetic test, StatinCheck, developed by Celera and offered through
Berkeley HeartLab, which is owned by Celera. It is now licensed by clinical labora-
tory of Aurora Health Care in Milwaukee, Wisconsin.
Physicians can use the KIF6 test to identify the increased risk for CHD and begin
treating their patients with statins. A study investigated whether 35 genetic poly-
morphisms, previously found to be associated with cardiovascular disease, were
associated with MI in the CARE (Cholesterol and Recurrent Events) trial and with
CHD in the WOSCOPS (West of Scotland Coronary Prevention Study). In both the
CARE and the WOSCOPS trials, carriers of the KIF6 719Arg allele had an increased
risk of coronary events, and pravastatin treatment substantially reduced that risk
(Iakoubova et al. 2008 ). Carriers of the 719Arg allele of KIF6 have 34 % higher risk
of MI and 24 % higher risk of CHD compared with noncarriers among 25,283
women from the Women’s Health Study, confi rming and extending previous reports
(Shiffman et al. 2008 ).
CE-marked KIF6 genotyping assay for use on Abbott Laboratories’ m2000 real-
time PCR platform is available in Europe to detect a genetic biomarker that may be
used in conjunction with clinical evaluation and patient assessment to identify indi-
viduals at risk for coronary heart disease and to treat patients with elevated choles-
terol, for whom statin treatment is being considered.
Role of Diagnostics in Personalized Management of Cardiovascular Disease