Both sex-based and ethnicity-based differences in the performance of MICRO-RNA biomarkers
Former DDA Visiting Professor, Dr. Ari Meerson from MIGAL, Galilee Research Institute in Israel, and his group have just published a new paper titled “Sex Differences in Plasma MicroRNA Biomarkers of Early and Complicated Diabetes Mellitus in Israeli Arab and Jewish Patients”. The study was a collaboration of researchers and clinicians in the Jewish and Arab sectors in Israel. To examine the performance of microRNA- based biomarkers of type 2 diabetes, they looked at the levels of candidate microRNA levels in the blood of patients with early and complicated diabetes.
They found both sex-based and ethnicity-based differences in the performance of microRNA biomarkers in their samples. These findings suggest that the design of microRNA biomarker panels for diabetes and complications should take sex and ethnicity into consideration.
Q and A with Dr. Ari Meerson
1) What kind of differences did you find with regard to ethnicity?
We found that the levels of a microRNA molecule, miR-183-5p, were elevated ~ 3-fold in the blood of Muslim Arab patients with early type 2 diabetes, but not in the Jewish patients at the same disease stage. This molecule also showed higher levels in the Arab group in general, regardless of disease status.
2) What kind of differences did you find as regards sex?
The sex differences were a lot more pronounced. When we looked at men and women together, there were hardly any blood microRNAs that could work as biomarkers - meaning that their levels change together, or correlate, with other clinical measurements. But when we looked at men and women as two separate groups, there were many strong associations between microRNA levels and clinical measurements, like glucose levels, cholesterol, and blood pressure. Most of these relationships were different between men and women. Take, for example, a microRNA molecule named miR-486-3p. In women its levels went up with higher LDL cholesterol. In men, however, its levels showed no correlation with LDL, but went down with higher HDL cholesterol.
3) Did the findings surprise you?
It’s no secret that men and women differ physiologically, both in health and disease. Therefore we expected to see some differences, especially between the sexes. However the extent of the differences was surprising to us. The ethnicity differences were more subtle, and could be caused by differences in lifestyle and nutrition rather than genetics.
4) What do these findings mean for future research as regards sex and ethnicity?
I think our results stress a simple point, which is a central premise of the push for personalized medicine, but which is nevertheless sometimes overlooked. Diagnostics, just like therapies, do not work the same way in different people. Sex, ethnicity, lifestyle, nutrition, individual genetics - all of these factors not only affect how a patient will respond to therapy, but also which biomarkers are informative regarding their health and disease.
5) What are your next steps concerning these findings?
It is important to test our results in other, and larger, patient cohorts to see how universal, and how large are the sex differences in the effectiveness of microRNA-based and other biomarkers of diabetes and complications. It is also important to find out how these differences come to be. What is the difference in the way that the microRNAs are expressed in the tissues and organs of men and women? Or in the way they are secreted into the blood stream? All these questions are still open.
6) Are your findings unprecedented or are they backed up by other studies?
Our findings are certainly not unprecedented; my guess is that many biomarker studies which include both men and women, will show differences between them, as long as one looks for these differences instead of just statistically adjusting the data for them. In fact, many studies seek to bypass this “problem” by looking only at men, or only at women. This approach is legitimate of course, but one has to remember that what you found is true for men, may not work at all for women, and vice versa.