Small changes in the sequence of genes can have a variety of biological impacts. Mutations that alter only one base pair of a gene may lead to serious diseases in some cases, while single base pair changes can also have very small effects, which might influence different traits in some cases. Some traits are affected by many genes, and thus, all the changes within those genes. Genome-wide association studies can reveal genetic variants that alter human health, and many have been discovered that may increase the risk of a complex trait, like cardiovascular disease. But researchers have now identified a genetic variant that seems to have a protective effect.
Reporting in Science, researchers analyzed genomic data from a population of Amish individuals. After assessing almost 7,000 genomes and the associated health data, the researchers found genetic variants that were linked to a reduction in the risk of cardiovascular disease. The variants seemed to prevent heart disease.
Heart disease is the leading cause of death worldwide. This research could help scientists develop therapeutics for heart disease, or preventive treatments that stop heart disease from progressing.
Abnormally high levels of molecules called fibrinogen, which is involved in blood clotting, and low-density lipoprotein cholesterol (LDL-C), have each been linked to the risk of cardiovascular disease. The levels of those molecules can be influenced by genetic variants, though not many have been found that exert an influence on more than one heart disease risk factor.
This study revealed a missense variant in a gene called B4GALT1. The rates of cardiovascular disease was reduced in carriers of that B4GALT1 vairant. When researchers modeled the variant in mice, they determined that there was a decrease in the level of LDL-C in the blood of the mice. There was also a reduction in fibrinogen, which suggests that this mechanism could be at work in people carrying the variant too. It may be possible to use what we now know about the genetic variant to create therapeutics for heart disease.
Sources: American Association for the Advancement of Science (AAAS), Science