We’ve all heard the basics. Eat healthy. Exercise. Sleep well. That helps, but for South Asians, it doesn’t fully explain why heart disease hits so hard and so early. Even people who do everything right still end up with clogged arteries or high cholesterol in their 30s or 40s. Something else is going on. That something is genetics.

 

South Asians are at higher risk for heart disease than most other groups. And while lifestyle matters, it’s not the full story. A lot of that risk comes from differences in our DNA. According to a study on genetic cholesterol, “The risk of ASCVD is 4.4- to 6.8-fold increased in patients with an [genetic cholesterol] variant compared with controls, depending on the severity of the DNA change.” (1) There are specific genes that control how your body handles fat and cholesterol. If you have certain mutations in genes like LDLR, PCSK9, or APOB, your cholesterol might stay high even if you eat healthy and work out. These mutations are more common in South Asians, but they’re often missed. That’s because most of the research behind genetic testing is based on European populations. So if a South Asian gets tested, the results might not be accurate. You might get told you’re fine when you’re not.

 

I talked to a genomics scientist who works on this. Her job is to look for these mutations in people’s DNA and figure out their disease risk. Her team sequences your DNA once, and they can keep going back to that same data to answer different questions. They look for changes in specific genes and use that info to flag people who might need treatment earlier than usual. For example, according to paper on genetic sequencing for cholesterol, “gene sequencing identified an FH mutation in <2%. However, for any observed LDL cholesterol, FH mutation carriers had substantially increased risk for CAD.” (2) Another paper on a gene called APOA1 (a important gene to look at when considering cholesterol) hypothisized that the “Characterization of polymorphisms in the APOA1 gene may well shed light on why South Asians are disproportionately affected by heart disease with ApoA-1 protein levels being the single most powerful predictor for the development of heart disease.” (3) But the field has problems. Insurance doesn’t usually cover genetic testing unless you’re already sick. Some people don’t want to share their genetic data because they’re worried about privacy. And even the labs doing this work aren’t always stable. Some have shut down. That makes it harder for people to get the info they need.

 

The biggest problem, though, is representation. Most studies still focus on white patients. That means everyone else, including South Asians, gets left out. Genomics isn’t the full answer but it fills in the blanks. For South Asians, those blanks matter. Heart disease doesn’t just show up randomly. Sometimes it’s written in your DNA. The sooner we start paying attention to that, the better we’ll be at staying ahead of it.

 

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Sources:

1. Khera, A. V., Won, H. H., Peloso, G. M., et al. (2019). Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia. Journal of the American College of Cardiology, 73(6), 712–722. https://pubmed.ncbi.nlm.nih.gov/30755017/

2. Abul-Husn, N. S., Manickam, K., Jones, L. K., et al. (2016). Genetic identification of familial hypercholesterolemia within a single U.S. health care system. Science, 354(6319). https://pubmed.ncbi.nlm.nih.gov/27050191/ 

3. Tiwari, H. K., Mudd, E. E., & Lin, H. Y. (2012). APOA1 polymorphisms as a marker for coronary artery disease among South Asians: A pilot study. Journal of Genetics, 91(3), 249–254. https://pubmed.ncbi.nlm.nih.gov/22345992/