Hearts of Healthy People with Gene Mutations ‘Primed to Fail’

Certain gene mutations can increase the risk of heart failure in healthy people, researchers report.

It had been believed that gene mutations in a protein called titin affect only people with dilated cardiomyopathy, one of the most common forms of inherited heart disease.

But this study of more than 1,400 adults found that the hearts of healthy people with mutations in the gene may be “primed to fail” if affected by other genetic or environmental factors. About 35 million people worldwide may be at risk, the researchers said.

“Our previous work showed that mutations in the titin gene are very common in people diagnosed with heart failure. Around 1% of the general population also carry these mutations, but until now it wasn’t known if these are ‘silent’ gene changes or changes that can adversely affect the heart,” said co-author Dr. Antonio de Marvao in a news release from imperial College London. He is a clinical lecturer at the college’s MRC Clinical Sciences Centre in England.

Study co-senior author Dr. Stuart Cook is a professor of cardiovascular medicine at SingHealth Duke-NUS Academic Medical Center in Singapore. He said, “We now know that the heart of a healthy individual with titin gene mutation lives in a compensated state and that the main heart pumping chamber is slightly bigger.

He said the next step is to identify the specific genetic or environmental triggers, such as alcohol or viral infection, that increase the risk of heart failure in people with titin mutations.



The study was published Nov. 21 in the journal Nature Genetics.

My Take:
There are no ‘silent’ gene changes, just those we don’t yet understand. The concept that 98.8% of our DNA is ‘junk DNA’ is a misnomer at best. These non-coding genes have a purpose. For example, we now know that every time a viral infection gets into your blood stream some of the viral DNA is incorporated into your non-coding DNA. This appears to enhance our immune system in ways we have yet to define.

When a heart chamber enlarges, it can have physiological advantages. This is common in endurance athletes. However, over time this also increases the odds of afib (atrial fibrillation) and other heart rhythm disorders. Cardio electrophysiology is the fasting growing discipline in cardiology as heart rhythm disorders are rapidly increasing in our nation. This gene mutation may provide a key to early diagnosis and treatment of these conditions.

One of the key environmental factors that needs to be examined is the use of statin drugs in this patient population. Studies indicate that 10% of patients taking statin drugs develop cardiomyopathy. Screening for the titin gene might help predict those patients at increased risk for side effects from the use of statin drugs to lower serum lipids.

Finally, as a side note, there is a simple blood test – the L(p)a - that identifies potential coronary risk better than any other serum lipid test. However, elevation of the L(p)a is a genetic factor and to date, no drug company has developed any medications to reduce the serum levels. Therefore, the test is seldom run. Fortunately, both the niacin flush and gingko leaf extract are extremely effective a lowering the L(p)a.

The Bottom Line:
This is very interesting research that stimulates one to extrapolate on the practical uses of such genetic testing. Genetic testing is at the forefront of research. Epigenetics, how we modify that genetic expression, is the future.

November 23, 2016 National Institutes of Health