Thailand medical study uncovers a rare genetic variant linked Brugada Syndrome

Thailand Medical: In a groundbreaking study, scientists from Thailand and several international institutions have identified a rare non-coding variant in the SCN5A gene that plays a crucial role in the high prevalence of Brugada Syndrome (BrS) in the country. BrS is a serious cardiac condition that can cause sudden death, particularly in young adults. This study not only highlights a unique genetic variant but also brings a deeper understanding of why Southeast Asia, particularly Thailand, has such a high rate of this disorder.


Thailand medical study uncovers a rare genetic variant linked Brugada Syndrome

What Is Brugada Syndrome?
Brugada Syndrome (BrS) is a rare but dangerous heart condition that disrupts the normal rhythm of the heart. It’s most notorious for its link to sudden death, especially among otherwise healthy young people. The condition often goes unnoticed until a person experiences life-threatening symptoms such as fainting, irregular heartbeats, or worse, sudden cardiac arrest.
 
Doctors use an electrocardiogram (ECG) to detect Brugada Syndrome by identifying abnormal patterns in heart activity. However, genetic factors also play a big role in who is at risk. And here’s where this new research comes in.
 
The Genetic Puzzle of Brugada Syndrome in Thailand
Until now, scientists didn’t fully understand why BrS is more common in Southeast Asia compared to Europe and other regions. This Medical News report uncovers that researchers from Chulalongkorn University in Thailand and Amsterdam University Medical Centers in the Netherlands have made a key discovery. They found that a rare genetic variant, hiding in a non-coding section of the SCN5A gene, is disproportionately present in Thai Brugada Syndrome patients.
 
The study included genome sequencing of 231 Thai individuals with Brugada Syndrome and 500 control participants. The researchers identified a specific enhancer variant in the SCN5A gene, which was found in 3.9% of Brugada Syndrome patients but only 0.2% of the control group. In terms of odds, people carrying this variant have an increased likelihood (20-45 times more!) of developing Brugada Syndrome compared to those without it.
 
Why Is This Important?
Well, most of the genetic variants linked to Brugada Syndrome are coding variants that directly affect protein function. But this variant? It’s a non-coding enhancer, meaning it doesn’t change the structure of the sodium channels that control heart rhythm. Instead, it messes with the gene's "switches" that control how much sodium channel protein gets made. In simpler terms, it's like finding out that the problem isn’t with the engine of your car, but with the fuel line.
 
To test their findings, the researchers used human-induced pluripotent stem cell-derived cardiomyocytes (fancy term for lab-grown heart cells) and introduced this variant. The results were pretty clear: the cells with the variant produced 30% less sodium current, which is crucial for maintaining a stable heart rhythm.&l t;br />  
Impacts of the Variant
For those carrying the variant, the consequences were severe. Around 89% of patients with this rare genetic change had experienced sudden cardiac arrest or other dangerous heart events, compared to 58% of Brugada Syndrome patients without it. That’s a big jump. On top of that, patients with this variant had larger epicardial substrate areas (i.e., abnormal areas in the heart muscle), making them more prone to heart rhythm problems.
 
These findings suggest that this variant significantly increases the risk of serious heart events, and may partly explain why Brugada Syndrome is so prevalent in Thailand. The SCN5A gene plays a central role in heart health, and this particular variant is a major factor in the region’s Brugada Syndrome cases.
 
The Bigger Picture: Genetics & Geography
What’s especially interesting about this discovery is that the variant seems to be unique to Thailand or Southeast Asia. When the researchers searched various genome databases from around the world, they couldn’t find the variant in European populations and only found it in 0.06% of the Thai population. This localized genetic factor could help explain why Brugada Syndrome is so much more common in Southeast Asia.
 
This also raises some intriguing questions. Are there other genetic traits in this region that could offer protection against other health risks? Could these same traits be making the population more vulnerable to Brugada Syndrome?
 
What Does This Mean for the Future?
The implications of this study are huge. Not only does it offer a potential explanation for the high rates of Brugada Syndrome in Thailand, but it also opens the door to new strategies for diagnosing and treating the condition. Genetic testing for this variant could help identify individuals at higher risk, giving doctors a better chance to prevent sudden cardiac deaths.
 
Moreover, this discovery highlights the importance of studying non-coding regions of the genome, which have often been overlooked. While coding variants have been the traditional focus, non-coding variants like the one found here could explain many of the so-called “missing heritability” in genetic diseases.
 
Conclusion: A Step Forward in Understanding BrS
In conclusion, this study is a major step forward in understanding the genetic basis of Brugada Syndrome, particularly in Thailand. By identifying a rare non-coding enhancer variant in the SCN5A gene, researchers have provided a crucial piece of the puzzle that could help explain why this deadly condition is so prevalent in Southeast Asia. The variant not only increases the risk of Brugada Syndrome but also causes significant reductions in sodium channel function, leading to a higher likelihood of sudden cardiac events.
 
These findings not only offer hope for improved diagnosis and treatment but also underscore the importance of genetic research in uncovering the mysteries of complex diseases. As science continues to delve into the non-coding regions of the genome, we may find that these “hidden” genetic elements hold the key to understanding many other conditions as well.
 
The study findings were published on a preprint server and is currently being peer reviewed.
https://www.medrxiv.org/content/10.1101/2023.12.19.23299785v1
 
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