FM SEPTEMBER 2018 ISSUE - digital edition

cardiogenetics
INHERITED HEART DISEASE
BIGGEST KILLER GETS
Despite the fact that genomic data help measure the risk precisely, inherited
heart diseases remain largely neglected
C H UNNIKRISHNAN
Cardiovascular disease has been the largest cause of death
in India for several decades. Although high blood pressure
and the buildup of fat inside the artery walls, contributed
by unhealthy diet, smoking, obesity and stress, are still singled
out as key risk factors, recent studies flag a more serious alert
on the genetic side. These studies have proved that around
4.5% of South Asian population are naturally prone to heart
disease. The cause is inherited genetic mutation. Of this group,
at least 10% are carriers of the same mutation from both the
parents and therefore run the risk of sudden cardiac death at a
very young age.
So, think before prescribing a blood thinner and giving a pat
on the patient’s shoulder saying there is a “small congestion”
in the heart. Do a fact check on the medical history of the
patient’s family and you ought to find similar cases there,
either living with the disease or involving death at a young
or middle age. Go a little deeper, as such cases often need a
comprehensive evaluation.
The prevalence of inherited heart diseases have been high
in the country, but unfortunately it hasn’t got much attention
until now. In today’s genomic era, population mapping and
next-generation sequencing technologies are revealing the true
and scary picture. If these studies are to be believed, around 60
million Indians carry a monogenic mutation that is responsible
for serious cardiomyopathies, a frequent cause of sudden heart
failure.
MyBPC3-key villain
While at least 200 rare mutations affecting more than 20
different genes have been identified for heart disease, the
mutation associated with the gene MyBPC3 or the sarcomeric
gene is found to be the key factor that causes dilated
cardiomyopathy (DCM) and hypertrophic cardiomyopathy
(HCM).
The MyBPC3 gene that provides instructions for making
cardiac myosin binding protein C (cardiac MyBP-C) is found in
heart muscle cells or sarcomere. This cell structure,
which is the basic unit that helps heart muscle contraction,
are made up of thick and thin filaments. The overlapping thick
and thin filaments attach to each other and release, which
allows the filaments to move relatively to one another so that
muscles can contract with a regular rhythm to pump blood to
the body. MyBP-C also regulates the speed of cardiac muscle
contract.
Because individuals who have heritable cardiomyopathies
with MyBP-C defects have a disorganised sarcomeric structure
and late-onset symptoms, MYBPC3 has been identified for
increased risk of heart failure by either hypertrophic or dilated
cardiomyopathies.
Earlier studies had identified variant(s) in MyBPC3
associated with increased risk of heart failure by screening
“More than 1.5 billion
people in South Asia are
correctly viewed not as a
single large population,
but as many small
endogamous groups.
Dr K Thangaraj
Senior Principal Scientist, CCMP,
Hyderabad.
There are multiple challenges here.
First is the low awareness about
inherited heart diseases, the other
two are the cost and general
inertia in approaching these
cases in a comprehensive way,
Dr Hisham Ahmed
Consultant Cardiologist, AIMS Kochi
18 / FUTURE MEDICINE / SEPTEMBER 2018