First Single Gene Mutation shown to result in Type 1 Diabetes

New York, NY, March 5, 2013 ? A JDRF-funded study out of Switzerland has shown that a single gene called SIRT1 may be involved in the development of type 1 diabetes (T1D) and other autoimmune diseases. The study, ?Identification of a SIRT1 Mutation in a Family with Type 1 Diabetes,? was published today in Cell Metabolism and represents the first demonstration of a monogenetic defect leading to the onset of T1D.


http://jdrf.org/press-releases/first-single-gene-mutation-shown-to-result-in-type-1-diabetes/


Christine

 

This sounds very interesting. I wonder how they can take this information and use it to cure Type 1 Diabetes? It will be interesting to watch how this unfolds. Thanks for posting.

 

Thanks for posting this Christine. It sounds really interesting.

Until now none of the monogenic forms of diabetes have resulted in autoimmune diabetes. They have generally been caused by an inability to produce, secrete or respond to insulin. As a result, although scientifically useful, the lessons to be learned from monogenic diabetes have been more likely to improve the treatment of Type 2 than Type 1.

This is different. In the family studied here the mutant gene seems to be the root cause of the autoimmune destruction of the beta cells. Normal SIRT1 is involved in regulating a wide range of genes by switching them off. It will be interesting if they can identify which genes are not being switched off in this family which may help us understand the basis of autoimmunity. The indications are that the key might be in the role of SIRT1 in damping down the inflammatory response. It has long been thought that autoimmunity may be related to inflammation.

Exciting times!

 

So in this case a 26 yr old is diagnosed with type 1, presumably has autoantibodies and his doctor doesnt just say "ok, type 1, lets call is a day," he actually investigates solely because of the strong family history. Thats pretty amazing.

 

I agree, this is very different. I'll be interested to see how this plays out in further research!

Christine

 

It is interesting, but I wonder how common this is, in the grand scheme of things? (especially since most of the monogenic types of diabetes aren't autoimmune). I know that there is great work being done with ER stress which I suspect is going to hold answers for both type 2 and type 1.

 

It sounds like a monogenic mutation as the cause of T1 is very rare, but the research may be helpful toward finding ways to enhance beta cell survival and function.


"Patricia Kilian, Ph.D., director of the Beta Cell Regeneration Program at JDRF, concurred, and said that the development is exciting for many reasons: While the change in the genetic makeup within this family with type 1 diabetes is rare, the discovery of the role of the SIRT1 pathway in affecting beta cells could help scientists find ways to enhance beta cell survival and function in more common forms of the disease. This study also reinforces increasing evidence that abnormal beta cell function has a role in the development of type 1 diabetes, and that blocking or reversing early stages of beta cell dysfunction may help prevent or significantly delay the disease's onset. Drug companies are already in the process of developing SIRT1 activators, which could eventually speed our ability to translate these new research findings into meaningful therapies for patients."

I agree with you about the work in ER stress being likely to be very helpful as well.


Christine

 

As Christine said it doesn't seem that common. In this study they tested 2000 diabetics (some sporadic and some familial) for the specific mutation found in this family and found none. Also in the many large scale genetic association studies (involving many thousands of patients and controls the SIRT1 region has not cropped up as a region of interest for Type 1 (although some Type 2 and BMI effects).

Having said that I think it might be interesting to sequence the whole SIRT1 gene, particularly in families with very strong inheritance of Type 1, to see if other mutations in the gene might be involved. I suspect this might be being done somewhere already.

It will be rare but studying the rare cases often tells us more about the more common cases. I like the quote by the 17th Century physician William Harvey, "Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of Nature by careful investigation of cases of rare forms of diseases. For it has been found in almost all things, that what they contain of useful or applicable nature is hardly perceived unless we are deprived of them, or they become deranged in some way"

 

oh, don't get me wrong, I fully believe that they are going to find loads more monogenic cases. There was a study I just posted the other day which showed that about 15% of the cases of type 1 are negative for antibodies, so what causes those? Most certainly a gene defect. I think that will be the key to unlock what's happening because most certainly they'll find, like in this case, there are genes responsible for causing autoimmune attacks. Something starts the process. The issue then becomes, on each gene, how many mutations are involved and is it different in each case.