DIO2 gene tests positive. Do we know what percentage please.

[McPammy]

Please do you know what percentage of people suffering with Hashimoto test positive with DIO2 gene test

I want to explain to my NHS Endocrinologist and my NHS GP who both have no clue about this test.

I’m due to see my NHS Endocrinologist soon. Last time he saw me 4 months ago he had just wrote a letter to my GP stating I needed a psychiatric assessment and not T3 medication!! I was not included in this letter but found it as I have patient access to my NHS records. I clearly needed T4 and T3 medication. I had a trial of T3 medication and it’s has been a huge success for my health.

I was just wondering if anyone has this information as I wanted to use it along with the positive result gene test report when I speak with him

Thank you.

[MaisieGray]

It depends to some extent, which polymorphism you are referring to. In a paper by Carlé et al for instance, they wrote "We investigated 3 single nucleotide polymorphisms (SNPs) on the type II iodothyronine deiodinase (DIO2) gene (rs225014 (Thr92Ala), rs225015, and rs12885300 (ORFa-Gly3Asp)) and 1 SNP on the cellular membrane transport-facilitating monocarboxylate transporter (MCT10) gene (rs17606253)" and went on to say "The polymorphisms investigated were rather common, judged by their MAF varying between 17 and 47%." I can't immediately find the full report, but the abstract of the WATTS study published by Panicker et al, it states "The rarer CC genotype of the rs225014 polymorphism in the deiodinase 2 gene (DIO2) was present in 16% of the study population". Please note, as far as I know, there is no differentiation made between all with hypothyroidism, and those with Hashimoto's.

[McPammy in reply to MaisieGray]

Thank you very much for replying with the details. I’m guessing it’s nit that easy to pin down. I had the DIO2 gene test which came back as :- DIO2 (T92A) rs255014 Heterozygous variant genotype TA. Decreased ability of the enzyme to generate the active T3 hormone.

I just wondered if Thyroid UK or any member had a percentage of how many people tested actually are positive.

Thank you so much for the info.

[MaisieGray in reply to McPammy]

Given that you tested positive for rs255014, you do have that figure now - 16%

[McPammy in reply to MaisieGray]

Yes sorry. I did mean to say thank you for that information. So now I know I’m in the 16% group. I will google Watts study if I can I read up on it all.

Thanks again MasieGray. 👍

[jimh111 in reply to MaisieGray]

Maisie, rs225014 Heterozygous is about 40%. Homozygous is about 16% (40/100 x 40/100). These are approximate percentages, the original study academic.oup.com/jcem/artic... found:

The rs225014 genotype frequencies were not significantly different between the two study groups (frequency of TT, TC, and CC genotypes: 40.6, 45.5, and 13.9%, respectively, in T4/T3 group and 41.1, 41.1, and 17.9% in T4 only group, P = 0.38).

The percentage with the rs225014 genotype varies within different population groups, e.g. based on ethnicity (or even locality if I remember correctly). The study found impaired baseline wellbeing and enhanced response to T4/T3 therapy in the homozygous group.

[SlowDragon Administrator in reply to jimh111]

Actually researchers found both Heterozygous and homozygous variation caused symptoms

thyroiduk.org.uk/tuk/testin...

The patients on this study were given T4 only for a set period and then combination treatment of both T4 and T3. The patients who had normal genes did not feel any different on combination treatment. However, those who had one faulty gene felt better on the combination treatment and those with both faulty genes felt better still.

[jimh111 in reply to SlowDragon]

The text you quote certainly appears on the thyroiduk webpage but is not in the study paper, nor anything like it. Here is the full paper academic.oup.com/jcem/artic... (the thyroiduk link doesn't work).

There is a statement:

'No significant differences were seen in the other psychological scores, although all the scores appeared to increase in the same direction across the genotypes (Table 3), with the TT genotype having the lowest score and TC intermediate and CC the worst score.'

which might be expected. However, the TC scores did not reach statistical significance compared with the TT patients who don't have the rs225014 polymorphism. So, possibly TC patients felt very slightly better on combined therapy but the study was unable to demonstrate this.

I think we should see this in context, patients homozygous for this polymorphism (CC) had slightly lower scores and responded to combined therapy. The trial subsituted 10 mcg L-T3 for 50 mcg L-T4 (it should be closer to a 1:3 ratio) so perhaps the combined group were slightly undermedicated. On the other hand 10 mcg L-T3 would more than fully compensate for the 6 mcg T3 secreted by the thyroid.

My personal view is that these polymorphisms are not very important. Patients should be given a little T3 to give a closer match to healthy thyroidal secretion (and perhaps a touch more to compensate for thyroidal T4 to T3 conversion). However, the effects of the polymorphism are quite small especially when compared to the severe signs and symptoms many patients have. I hope to publish a possible explanation of why this happens in a week or two.