Way back in the distant and hazy past of 2009 I wrote about a company called Juneau Biosciences who were looking to recruit women with endometriosis for genetic research study. Well the results are in and they have released a preliminary report on what they have found.
The report states that they have found mutations in an imprinted gene called NLRP2 that are more common in women with endometriosis. What does this mean? Well, that will be the subject of todays blogpost.
First of all we need to understand what an imprinted gene is and why they are important. I’ve wrote before about genes, what they are and how they work, but what are imprinted genes? Normally a child inherits two ‘active’ copies of each gene, one from the mother and one from the father. However in some cases one of the genes, from either the father or the mother, can be switched off or ‘imprinted’ meaning that the child only has one working copy of the gene. This makes imprinted genes more ‘vulnerable’ because normally there would be two working copies of each gene, so if one copy gets mutated or stops working, there is a backup copy. With imprinted genes there is no backup, so if that gene has an important function (like preventing a cell becoming cancerous, for example) then there is a greater risk of a deleterious effect occurring.
Onto the next question, what does NLRP2 gene do and why is that relevant to endometriosis? The products of NLRP genes, in general, have a role in regulating the immune system and inflammation, which may be their most relevant known function in endometriosis. In particular NLRP2 has been shown to inhibit some key mediators of inflammation. Endometriosis is characterised by an increase in inflammation, both around the lesions and throughout the whole body (it is even thought that this might contribute to the fatigue many women with endometriosis experience). Also, I have written previously about how women with endo are at a higher risk of certain inflammatory and immune conditions, like inflammatory bowel disease, allergies and asthma to name a few. So finding alterations in a gene that is involved in inflammation and the immune system is potentially quite intriguing.
It could be tempting to suggest that this new finding could go some way to explaining why there is excess inflammation in endometriosis. However the sheer number of factors that contribute to the regulation of inflammation in endometriosis is huge (and still not fully understood) so exactly how significant a single factor is remains to be seen (in any case, the exact role of NLRP2 in general has been poorly characterised). Another point is that we need to know how these mutations in the NLRP2 gene affect the function of the protein it produces.
So there is a way still to go before this research can be translated into something relevant for the women living with endometriosis, but all progress needs a starting point, and this is a pretty good starting point.