However, there is a trade-off where the same variability is also associated with increased autoimmune diseases.
Previous research has shown that survivors of the Black Death, a devastating bubonic plague pandemic in the Middle Ages, were more likely than non-survivors to carry certain variants, called alleles, in a gene called ERAP2.
What does gene mean?
The gene is considered the basic unit of heredity. Genes are passed from parents to offspring and contain the information needed to determine physical and biological characteristics. Most genes encode specific proteins or segments of proteins that have different functions in the body. Humans have about 20,000 protein-coding genes.
In a new study published in The American Journal of Human Genetics, Dr. Fergus Hamilton and co-authors from the university’s MRC Integrative Epidemiology Unit (MRC IEU) are collaborating with colleagues at the universities of Edinburgh, Oxford, Cardiff and Imperial College London. , reveals that the same variants exist in humans today and provide similar protection against not only bubonic plague, but also other infections, including pneumonia and COVID-19. However, this is a state of equilibrium, and the same genetic makeup is likely to be associated with an increase in various autoimmune diseases.
Same Gene, Different Functions
Lead author Dr. “This gene basically breaks down proteins for the immune system,” Hamilton explained. “Although we do not know the exact mechanism that affects disease risk, carriers of alleles that confer greater protection against respiratory diseases have an increased risk of autoimmune disease. This is potentially a great example of a phenomenon called ‘balancing selection’ – where the same allele has different effects on different diseases.”
Dr. Hamilton and colleagues looked at infection, autoimmune diseases, and parental longevity among participants in three large contemporary genetic studies. They used an analytical technique known as Mendelian Randomization to find associations between variations in the ERAP2 gene and the risk of autoimmune disease and infection.
Their findings point to antagonistic effects between these two groups of diseases caused by pressures that may be more or less present in different human periods.
Nicholas Timpson, MRC IEU Professor of Genetic Epidemiology and co-author, added: “This is a theoretical balance story that reflects our past and relates to historical and contemporary disease profiles that are rarely seen in real human samples.”
What it means for future treatments
Determining the link between genetics and disease susceptibility may lead to potential treatments. However, it also highlights potential problems; Therapeutics targeting ERAP2 are currently being developed to target Crohn’s disease and cancer, so it is important to consider the potential effects of these agents on infection risk.
- ERAP2 mutation reverses severe respiratory infections and autoimmune diseases – (https:pubmed.ncbi.nlm.nih.gov/36889308/)