Sunday, 22 April 2012

Is Dupuytren's in your DNA?

As many of you will know I am in a science based job and I did my undergraduate degree in Molecular Genetics. Today I want to cover whether there is a genetic element to Ledderhose and Dupuytren's. As always the information available on Ledderhose is not there and so I am looking at Dupuytren's as if this is a predisposition at the genetic level then it seems likely that this is the same for both.

I felt that a good place to start here is the book - Dupuytren's Disease and Related Hyperproliferative disorders where: 

Chapter 11 - The Genetic Basis of Dupuytren's: An introduction: 

First of all they start by saying that virtually all diseases are a combination of Hereditary and environmental factors and from this I am concluding that this is why it is capable of skipping generations or like in my Ledderhose popping up from nowhere.

The familial incidence of this disease does vary and in Scotland, Sweden, Iceland and Norway for example it is high and several papers have put it as high as 44% and 74% (Skoog 1948 and Gudmundsson et al 2000) They also look in a variety of ways at 1000 patients in a study themselves where they observe that 40% of these have a family history of the disease although I cannot see any note of how recent this family history needs to be they do note that in these cases onset seems to be earlier and develop quicker. Interestingly, bearing in mind other posts that I have done on susceptibility, they do see 11% of cases with diabetes but there is NO link to alcohol or smoking.

From my point of view it makes some sense that if you have a family history you are more likely to suffer from this earlier. I think this because if you do have a genetic background that means then the balance between hereditary and environment is already heavily shifted towards you getting it so that only a slight environmental factor such as trauma, that in most cases would not result in the development of these diseases does for you because of the increased chance you have.

In their concluding comments of this section they do state that there are on-going studies where many countries are collaborating to try and tease out some of the mutations that might lead to increased odds of Dupuytren's and Ledderhose.

Interestingly research has already been done to look into some of the obvious candidates such as TGF-beta (see my picture at the bottom of this post as to why looking at this makes sense) and actually they have not seen a link between the two. This means that the problem lies elsewhere. In Chapter 12 this is discussed further to show that not only have they look at TGF-Beta but other members of that pathway and again no link is seen. This is somewhat surprising as on the one hand you would think that an increased level of TGF-B would result in an increased likelihood of Dupuytren's but all that the above results mean is that this cannot initiate the disease and but I reckon a higher level of TGF would result at least in faster progression of the disease.

It is obvious that there is some genetic element and that it some cases it plays a huge role, in some cases entire countries seem to be at risk once they have reached 50 and I guess these countries are where this research needs to be continued.

Genetics is not the be all and end all of getting these diseases, I on the one hand have no history of either Ledderhose or Dupuytren's but I have spoken to several people with extensive backgrounds of the disease. Yet in all the people I have spoken to only 1 has had a younger age of onset and they had a clear case of massive trauma to the site shortly beforehand. So although there clearly is an increased risk of getting a bent finger or a lump in your foot if you Mum and Dad did, if they didn't it doesn't mean you're safe.