In scientific research, men and women should be looked at separately by default. This is what Robin Hartman argues for. In his research at UMC Utrecht, he shows that the biological differences between men and women are greater than thought. After all, gender appears to influence gene regulation: the switching on and off of genes in cells. This undoubtedly has consequences for the treatment of diseases. On November 26, Robin received his doctorate for his research.
The biological differences between men and women consist of different sex chromosomes (XX in women and XY in men) and different sex hormones (estrogens in women and testosterone in men). These biological differences contribute to different disease development between men and women. A good example is the more frequent occurrence of non-reproductive cancer in men, and the more frequent occurrence of autoimmune diseases in women. There are also differences in development of arteriosclerosis, or atherosclerosis.
Robin explains: “We already knew that in atherosclerosis, women are more likely to develop stable plaques and men are more likely to develop unstable plaques. But the underlying biology of it, we did not know. My thesis shows that gender affects gene regulation; the switching on and off of genes in cells. That affects the tissue, which could explain why atherosclerosis in men tends to center around inflammatory responses, while in women with arterial calcification, the smooth muscle cell is more central. In any case, it is clear that a different cell biology plays a role in men and women.”
Part of his research included an analysis of recent literature on gene regulation in cardiovascular disease. “Of the 3071 studies that came back with our search term in a literature database, we found only 75 studies in which both men and women participated. And of those 75, only 13 were looking at men’s and women’s data separately.” Robin then looked at whether those differences in gene regulation change over the course of life. He examined endothelial cells just after birth in twins consisting of a boy and a girl. This showed that 14 to 25 percent of RNA patterns – a step in gene regulation – were subject to sex. “Later we found that these different RNA patterns also differed in adulthood and were involved in the development of arterial calcification.”
To see if this different gene regulation in men and women also affects other types of tissues, Robin and his colleagues looked at 24 different types of tissues. “Again, this showed that gender affects the activity of genes, namely in over 20 percent of the more than 13,000 genes studied across 24 tissues. Differences were greater in some tissues than others, but differences were apparent in all tissues studied. Male- and female-specific genes were involved in different processes in the cell, from inflammatory responses to the response of cells to low concentrations of oxygen.”
All this leads to one clear conclusion: women’s biology is different from men’s. Every scientific study, according to Robin, should therefore include as many women as men and describe the results separately. “From that, better treatments can come for both women and men.” To make that happen, doctors and researchers need to be trained in this and research institutes need to organize their research differently. As far as Robin is concerned, this should happen as soon as possible.
On Nov. 26, Robin Hartman received his doctorate with the thesis entitled: Sex and gene regulation in cardiovascular health and disease. The research was funded by the Heart Foundation.
