Association of the polymorphisms in the gene encoding thyroglobulin with the development and prognosis of autoimmune thyroid disease

[helvella]

The other day we heard Sally Davies saying that she wants and expects gene sequences for all cancer patients. (E.g. healthunlocked.com/thyroidu...... and other posts in the past few days.)

Now a paper identifies several genetic components that are at least associated with Hashimoto's and/or Graves and their disease courses.

I'd like to think the simple fact that thyroid patients typically suffer for decades would be a very strong argument in favour of gene sequencing. If knowledge of the genetic make-up of the individual can provide insight into their disease, suggest even marginal improvements in treatment, etc., those pluses are multiplied by so many years... Could we ever see the concept of quality-adjusted life decades being used to justify better healthcare? And how much would they be "worth"?

For any who ask, no, I don't understand genetics any better than you!

Autoimmunity. 2017 Jul 4:1-7. doi: 10.1080/08916934.2017.1344971. [Epub ahead of print]

Association of the polymorphisms in the gene encoding thyroglobulin with the development and prognosis of autoimmune thyroid disease.

Mizuma T1, Watanabe M1, Inoue N1,2, Arakawa Y1, Tomari S1, Hidaka Y2, Iwatani Y1.

Author information

1 a Department of Biomedical Informatics, Division of Health Sciences , Osaka University Graduate School of Medicine , Osaka , Japan.

2 b Laboratory for Clinical Investigation , Osaka University Hospital , Osaka , Japan.

Abstract

Graves' disease (GD) and Hashimoto's disease (HD) are autoimmune thyroid diseases (AITDs), and the prognosis of AITDs is different for each patient. We examined the association of polymorphisms in the Thyroglobulin (TG) gene with the pathogenesis of AITD. We genotyped TG rs180195G/A, rs853326G/A, rs2076740C/T, rs2703013G/T, rs2958692C/T and rs733735A/G polymorphisms in 137 HD patients, 131 GD patients and 89 healthy controls and also examined the levels of TG mRNA expression and serum TG. The TG rs180195 GG genotype was more frequent in HD patients (p = .0277), and the proportion of CD4+ cells with high levels of TG mRNA was greater in individuals with the GG genotype than in A carriers (p = .0107). The TG rs2703013 TT genotype was less frequent in AITD (p = .0186), and serum TG levels were lower in individuals with the TT genotype than in G carriers (p = .0170). In the TG rs2958692 polymorphism, the T allele was more frequent in intractable GD than in GD in remission (p = .0055), and serum titres of anti-thyroglobulin antibody (TgAb) were lower in GD patients with the TT genotype than in C carriers (p = .0151). In the TG rs2076740 polymorphism, serum titres of TgAb were higher in HD patients who were T carriers than in those with the CC genotype (p = .0359). SNPs in the TG gene were associated with the development of HD and GD, the intractability of GD, and the levels of TG mRNA expression, serum TG, and serum TgAb.

KEYWORDS:

Graves’ disease; Hashimoto’s disease; Thyroglobulin; polymorphism; severity

PMID: 28675712

DOI: 10.1080/08916934.2017.1344971

ncbi.nlm.nih.gov/pubmed/286...

[loueldhen]

As usual with these papers I rush off to my 23andme data and either the particular SNP is 'not found' or 'not genotyped'. One day I'll make sense of it all...... Thanks anyway.

[cwill in reply to loueldhen]

So that answers my question. I think that gene testing seems to be the Wild West of medicine rather than enabling us to get personalised medicine. And how is the NHS to afford to do the tests when we can't even get FT3?

[Hidden]

Having done family history and asking family members it would be no surprise to me that genetics for autoimmune disease is high in my family. Yes, I have Hashimoto's plus other autoimmune problems. Let's hope future generations get the help. GG

[JGBH]

Indeed it would be so useful to so many people... but thyroid problems don't make the headlines.... and no or little money is awarded for research in thyroid dysfunction.... not a "sexy" topic, to use today's expression...

[bluebug]

The problem of what Sally Davies is reported as saying is not that you, I or anyone else gets their genes sequenced to help us with our medical issues it is how that data is shared and used.

Already the Royal Free Hospital in London has been told off by the Office of the Information Commissioner (ICO) due to giving some cancer patient data to Google, for Google's own commercial ends. The patients are identifiable. The patients haven't been informed their data would be shared and possibly used in this way, and neither the Royal Free Hospital or Google have been fined by the ICO for this.

So yes it is a good idea to share DNA so genes can be found to improve treatment but we all should have a choice on who gets our personal info and we should be told how anonymous any shared data is. I've been told by a few people how poor the NHS is at anonymising data.

[helvella in reply to bluebug]

I certainly agree that managing access is a vital part of the whole process.

I'd add that if my permission is required for anything (access to my data, taking samples, pretty much anything), it seems absolutely iniquitous that papers subsequently published could be behind a paywall. A fundamental requirement should be that subjects always have free access. Furthermore, any papers based on NHS data (personal or collective) should be freely accessible to those who pay for the service and contribute their data - UK citizens.

[startagaingirl]

Hi - declaring upfront that I know a bit about genetics, since I am one of those who has been in the loop for personal and familial cancer. In fact I still am, my entire genome is now being mapped for the 100,000 genome project and I have also declared personal and family history of Hashis for this, so in some small part I may contribute to research such as that above! I know some of the foremost world experts in genetic research and it is still in its infancy as a science and understanding how different variations in different genes affect risks of different diseases. Even with the highlight on cancer, for instance, they are really only scratching the surface still and new discoveries are being made all the time. Even then, full understanding of what these mean is long, slow, painstaking work. But it is definitely going to have an increasing influence on medicine in the future.

Btw Helvella, I have sat through several lectures from health economists on qualys and it is not the most riveting of subjects - I think you need to be a real statistics geek to enjoy those!

Gillian

[Saggyuk]

Hmmm, I suppose I may just be too cynical and believe it could just as easily be used like issues such as CFS doc - "yeah nothing I can do to help as it's just your genes I'm afraid, I can give you some ADs to make you feel better about it though" lol!! Plus it may be used against you before genes have even been triggered.

That's the other problem - genes don't have to be triggered and may never do so. For example, my apparent thyroid genes triggered as a young teen, my mum whom also seems to have said genes didn't trigger until this year in her late 50s so I think working out what is triggering them and possibilities into untriggering them (if at all possible) is more important than individual gene sequencing. And I suppose the likeliest causes are already known using common sense really aren't they? I do think more individual knowledge of things that don't suit our system specifically would be useful though.

Although, if genetic expression is unavoidable, then I imagine they will become more widespread anyway in which case if the majority have these problems, it is less likely to be used against you lol. For example, many genetic faults/issues would have been self limiting - I never would have been able to have kids a hundred years ago not even taking my rhesus neg issues into account on top so the fact that medical intervention has allowed me too means I am spreading the genes unnaturally and will become more prevalent. The same applies to rhesus neg actually lol - we are now set on course to not be less common in the future and just as many people will be rhesus neg as rhesus pos at some point.

Genes are a funny thing really and there's soooo much more we need to learn about everything. I think they work on a level we may never really understand. I never really trust any scientific or medical breakthroughs/weird new treatments no one understand as often always found to be detrimental in the long run as they never take nature into consideration.

And gene therapy - wow that's another step entirely that I believe should never be messed with. Maybe yes to those very specific genetic malfunction where a single gene mutation can be identified or gene is completely missing etc but not on this kind of level as they have so many interactions with other genes. I actually have one of those severely rare messed up individual gene mutations in my family that I've been blessed to have missed and was able to deduce that I was not a carrier so do understand. However, many genes are there for good reason even if not apparent at first or within our realms of understanding at this point in time. Take sickle cell anaemia for instance. Yes, it's not nice to have it and seems totally wrong but in natures point of view, it is protective and actually increased the survival of populations.

Although, this is just my opinion and certainly way off being based on medical fact lol!!

[bluebug]

The Daily Mail published an update article which counters Sally Davies idea - dailymail.co.uk/news/articl...

[helvella in reply to bluebug]

Yes - it is far more complicated than just knowing a few genes. Yes - privacy and security issues are vitally important.

We already know that genes such as DIO2 have an impact in thyroid disorders (and others) - but we cannot usually get any medics to grasp that nettle. I think that would be the stumbling block for many years even if every other issue were to be satisfactorily resolved.