Heredity/Evolution English
2018-03-15 00:00:00
Vittorio Hernandez

There are now 22 known genes that are considered genetic risk factors for stroke. The number tripled after researchers held the MEGASTROKE study which was published on Tuesday in the Nature Genetics journal.

For the research, the scientists studied the DNA of more than 520,000 people all over the world. They compared the genes of patients who suffered different types of strokes with those of healthy volunteers.

New ways of increasing risk

The researchers said that around one-third of the newly discovered genetic variants, which are different versions of a gene, are believed to increase the risk of stroke by increasing a patient’s blood pressure. But the remaining two-thirds appear to hike the risk of a stroke in completely new ways. The other genetic influences include coronary artery disease and venous thromboembolism.

They said that one specific gene boosted a person’s risk of two very different types of stroke. These are the hemorrhagic stroke in which a blood vessel bursts and bleeds into the brain, and the ischemic stroke in which the blood supply to the brain is blocked by a blood clot.

The discovery could open the door for a new medication to help cut the risk of a person suffering from the two common types of stroke, the British Heart Foundation reported. Sir Nilesh Samani, the medical director of BHF, said that by helping the foundation better understand what causes a stroke, the study will help cardiologists prevent it from occurring and to develop desperately needed new treatments that could ultimately save lives.

He noted that despite the availability of exciting new developments in treating strokes, which includes clot-bursting treatment and clot retrieval devices, the options at the disposal of doctors for the treatment and prevention of strokes are still far too limited.

In the UK, around 38,000 people die each year after suffering a stroke. Of those who survived, there are 1.2 million people living with the cruel and debilitating after-effects of the ailment.

Biology and pathways leading to stroke

The study provided extensive novel insight on the biology and pathways leading to stroke. Professor Martin Dichgans, the director of the Institute for Stroke and Dementia Research at the Ludwig Maximilians-University in Germany, pointed out that the extent to which individual variants modify stroke risk is very small.

It requires a large number of subjects to discover those variants. But the university leveraged extensive datasets established by numerous researchers over the past few years. Stephanie Debette, a professor from the University of Bordeaux and Bordeaux University Hospital in France, emphasized the value of international collaboration across different ethnic origins when conducting a study of the genetics of complex, common diseases such as stroke.

The researchers based their study on DNA samples of 520,000 European, North American, South Americans, Asian, African, and Australian participants. Of the total number, 67,000 had a stroke, Sci-News reported.

Development of stroke drug

Dr. Susha Seshadri from the University of Texas Health Sciences Center, San Antonio said that the identification of genetic regions strongly correlated to stroke will boost potential targets for the development of stroke drugs. The researchers identified 32 genomic regions associated with stroke from the millions of genetic variants they analyzed. Two-thirds of the genomic regions were novel.

Seshadri explained that strokes can begin from alterations in different parts of the vasculature, including the large arteries, small arteries, the heart, and the venous system. The researchers found that genetic risk factors were implicated in each of these mechanisms.

Some of the genetic risk factors contributed to specific mechanisms, while others to stroke susceptibility at large. Among the significant discoveries of the researchers is that shared genetic influences between stroke caused by vessel occlusion – which is the most common cause of stroke – and stroke caused by the rupture of a blood vessel – which is the most catastrophic cause of stroke – are often thought to have opposite mechanisms.

But when the researchers studied closely the genomic areas pinpointed in the study, they observed that several of these overlap with genomic areas known to be implicated in related vascular conditions. It included atrial fibrillation, coronary artery disease, venous thrombosis, or vascular risk factors, particularly hypertension and less so, hyperlipidemia.

When the scientist added data on gene expression, protein expression, and other characteristics in multiple cell types and tissues, they got first insights into the specific genes, molecular pathways, and cell and tissue types through which the new genetic risk factors can cause a stroke.

They also discovered that the genes which were identified as enriched in drug targets for antithrombotic therapy are used to re-open occluded blood vessels in patients with acute stroke or to prevent vascular events, including stroke.

Dr. Bradford Worrall, a researcher at the University of Virginia School of Medicine, said these findings show the potential of genetics for drug discovery. Seshardri added that vascular disease in the brain, which is a series of strokes, can lead to dementia. By understanding these newly identified risk factors for stroke, it should enable the medical community to also find novel treatments for dementia.

[researchpaper 리서치페이퍼= Vittorio Hernandez 기자]

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