Three genes that today are associated with coeliac disease, an allergic disorder, turn out to have protected mankind for ages from certain types of bacterial infection. This follows from a large international study led by professor of genetics Cisca Wijmenga of the University Medical Center of the University of Groningen, conducted in collaboration with UMC Utrecht and UMC St Radboud. The research is published today in the renowned American Journal of Human Genetics.
Coeliac disease is an autoimmune disorder affecting 1-2% of the Western population. At present, about forty gene variants are known to be involved in the development of coeliac disease. These variants are widespread.
As yet it is not clear why these associated genes tend to dominate, since in the past coeliac disease must have had a negative influence on an individual’s chances of survival. Since the 1950s, coeliac disease can be treated with a gluten-free diet. Before then, the disease would often lead to reduced fertility and premature death.
It is therefore remarkable that the gene variants associated with coeliac disease were able to become so widespread in the population. The study was inspired by the thought that the genes now associated with coeliac disease must at some point have played a positive role in man’s evolution.
Wijmenga researched whether ten genes associated with coeliac disease could perhaps have offered an evolutionary advantage. She did so by investigating whether certain gene variants had left an evolutionary footprint in our DNA.
The central question in her research was whether these gene variants occurred more often than was to be expected, given their history. This did indeed turn out to be the case for three of the ten gene variants, SH2B3, IL18RAP, and IL12A respectively. The genes thus probably provided a survival advantage. The SH2B3 coeliac disease risk gene in particular was proven by the research to provide carriers with better protection against bacterial infection.
The evolutionary advantage existed in the era 1200 to 1700 years ago. ‘Unfortunately, we don’t know against which infections the SH2B3 gene provided protection. It could have been tuberculosis, but bubonic plague is also an option’, according to Wijmenga. ‘It’s a curious fact that mankind was able to survive these infections thanks to the presence of certain gene variants. The price we have to pay for this is the development of autoimmune disorders like coeliac disease.’
