This study provides scientific evidence linking 2 genes, GDF15 and IGFBP7, to HG. These genes provide the instructions to build the proteins GDF15 and IGFBP7 in the human placenta during pregnancy. The proteins are known to be important in the development of the placenta and in controlling appetite. We have done additional work presented at the ICHG (vimeo.com/260389622) showing that not only are these genes linked to HG, but also, the proteins are abnormally high in the blood from patients hospitalized with HG.
This suggests that the DNA instructions in some HG patients are telling the placenta to make too much GDF15 and IGFBP7 protein, which then gets into the mother’s blood, and causes extreme nausea and vomiting. This information provides strong evidence that these proteins are directly involved in causing HG. It puts an end to the unfortunate misogynistic nonsense that HG is “all in your head.”
Read full article: www.nature.com/articles/s41467-018-03258-0
There are many reasons you may not see HG in your family. One explanation is that it may be that the genes are passed on through your father. Another is that it may be that you need to inherit a certain combination of gene variants coming from one or both of your parents. Also, there may be other ways in addition to genetics that we don’t understand yet to explain why women with HG end up with too much GDF15 and IGFBP7 in their blood.
Related article: Familial Link of HG
We do not have a test yet. Getting FDA approval is a long process and this is just the beginning. We still have a lot to learn. Having the 2 variants that were confirmed in the paper increases the risk of having HG. It does not mean that if you have these variations in your DNA you will have HG and vise versa. And, it does not mean that if you do NOT have them, you will NOT get HG. There is still a lot of work we need to do to understand the genetic component, but this provides a very promising starting point. There are also other genetic risk factors that the study pointed to that we did not have funding to confirm, so this is not the end of the story. It is a new beginning.
Related article: 23andme
We do not have the answer to this question yet. We know that over 80% of women will have a recurrence, and we do not understand what is going on in those lucky 20%. One theory is that if you have the HG gene(s) and your baby inherits them, then that may increase the risk of an HG pregnancy, while if your baby does not inherit the risk genes, then you may have less severe symptoms. The placenta, which produces GDF15 and IGFBP7, is made up of both maternal and fetal tissue (and genes), so both mother and baby may be contributing to the abnormally high protein levels. We would like to test this theory but we do not have funding to collect DNA from HG babies and children.
Related article: Science Mag
So far, we have found that there are abnormal levels of GDF15 and IGFBP7 in the blood of women hospitalized with HG. We have more work to do to understand how common this is for HG patients and what the cut-off levels are for HG versus normal nausea and vomiting in the blood of pregnant women. Eventually this could lead to a test similar to a pregnancy test. This will take time.
Related article: Recurrence Risk HG
Cachexia is a condition characterized by the same symptoms as HG, nausea and vomiting, weight loss, muscle wasting, and extreme debility. Cachexia is the cause of death in 20% of cancer patients. Until now we did not know that HG and cachexia are biologically related. This is very good for HG because while research and investment in HG is minimal, there is a lot of interest in developing treatments for cachexia. A mouse model of cancer cachexia treated with a drug blocking GDF15 has already shown great promise. The drug restored appetite and weight gain in the mouse. If this drug is safe in pregnancy, it could be a very promising strategy for treating HG.
Related article: Live Science
These findings provide the most promising avenue to date for developing a treatment for HG. Now that we know GDF15 and IGFBP7 are involved, we can start thinking about what might be the best way to lower the levels of these factors in HG patients. Of particular interest, a drug blocking GDF15 has successfully restored appetite and weight gain in a mouse model with abnormally high levels of GDF15, so if it is safe in pregnancy, this holds much promise for HG. But I would like to caution that making and testing a drug for pregnant women is a very long and difficult process, so knowing whether this strategy will be successful is a long way off.
Related article: Science Daily
The study did not only look at HG. It also looked at different levels of nausea and vomiting from none, slight, moderate, severe, and very severe (HG). The study suggests that the same genes, GDF15 and IGFBP7, involved in HG are also involved in normal nausea and vomiting. Basically if you have these genetic variations that are linked to HG, you are more likely to have normal nausea and vomiting than no nausea and vomiting, and more likely to have HG than normal nausea and vomiting. Basically having the genes increases your risk, but ultimately it is likely the level of the proteins that is causal, which may vary depending on the genes and other factors that we still do not understand.
Related article: Genomeweb
We now have evidence that HG is caused by a combination of genetics and other factors. The greatest genetic risk factor for HG is variation in a gene that codes for the placenta and appetite hormone GDF15. Other genes are also associated with HG including a gene, GFRAL, that codes for the receptor of GDF15 in the vomiting center of the brain, the progesterone receptor PGR, and another placenta and appetite gene, IGFBP7. You inherit one copy of each of these genes from your biological mother and one copy from your biological father. You may not see HG in your family even if you have inherited the genes because you may have inherited them from your father, or you may need to inherit a combination of the genes mentioned above in order to get HG. Your mother may pass on one part of the combination, and your father the other.
In addition, there are other things besides genes that may contribute to HG. For example, we know that abnormal levels of GDF15 cause nausea, vomiting, and weight loss. But genetics is not the only factor that can increase GDF15 levels. We now know that other things also cause your body to produce more GDF15 hormone including nutrient deprivation, hyperthyroidism, potassium depletion, and infection. We still have a lot to learn, but for now we believe, abnormal levels of the GDF15 hormone play a big role regardless of whether the abnormal levels come from inheriting gene(s) from your mom, dad, both and/or from other factors.