Thyroid: Genetic Variants Report

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Genetics plays a role in your natural thyroid hormone levels as well as your susceptibility to hypothyroidism.  While all of the genetic variants below have been shown in studies to affect the thyroid, please keep in mind that this is a complex system so your results may vary.  If you have a thyroid problem, knowing where your genetic susceptibility lies may help you (and your doc) figure out solutions for you.

Please note that 23andMe changed the sequencing chip that they use for running their DNA tests in mid-July/August 2017.  If you have data after that time, your results are from the version 5 chip.  The genetic variants below include information about the chip (v.4 and/or v.5) on which they are found.

These reports are offered on a ‘pay what you can’ basis:



Genes Involved:

The PDE8B gene polymorphism is associated with TSH levels, specifically in those of European descent.[ref]

SNP Possible Variants Your Genotype
rs4704397 (v.4, v.5) AA: increase of 0.26 uIU/ml in serum TSH [ref]
AG: increase of 0.13 uIU/ml in serum TSH
GG: no increase in serum TSH
rs6885099 (v.4, v.5) AA: increased serum TSH [ref]
AG: increased serum TSH
GG: normal serum TSH

DIO1, DIO2 – Deiodinase genes for conversion of storage (T4) to active (T3)

The deiodinase 1 (DIO1) gene encodes a protein that converts T4 to T3 and is involved in the degradation of both T3 and T4.  Iodine and selenium are involved in these reactions.  [ref]  DIO2 is also involved in the conversion of T4 to T3.

SNP Possible Variants Your Genotype
rs2235544 (v.4, v.5) AA: decrease ratio of fT3 to fT4, decreased free T3  [ref]
AC: increased free T3: decreased free T4
CC: increased free T3: decreased free T4 [ref]
rs11206244 (v.4, v.5) TT: higher rT3, lower free T3  [ref]
CT: lower T3
CC: normal
rs225014 (v.4) CC: decreased DIO2 enzyme (T4 to T3 conversion)  [ref]
CT: decreased T4 to T3 conversion
TT: normal DIO2 enzyme

TSHR gene
Thyroid stimulating hormone receptor (TSHR) gene codes for a receptor protein that controls thyroid cell metabolism. [ref]

SNP Possible Variants Your Genotype
rs1991517 (v.4) CC: Normal
CG: slightly lower average TSH
GG: slightly lower average TSH [ref]
rs179247 (v.4) AA: increased risk (slightly) of Grave’s [ref]
AG: increased risk (slight) of Grave’s
GG: normal risk of Grave’s

The FOXE1 gene (thyroid specific forkhead transcription factor) has also been identified to increase the risk of primary hypothyroidism. [ref]

SNP Possible Variants Your Genotype
rs7850258 (v.4, v.5) AA: Lower odds of hypothyroidism (OR = 0.74)  [ref]
AG: Typical odds of hypothyroidism
GG: Slightly higher odds of hypothyroidism
rs965513 (v.4, v.5) AA: decreased TSH, increased risk of thyroid cancer[ref]
AG: decreased TSH
GG: normal
rs925489 (v.4, v.5) CC: decreased risk of hypothyroidism[ref]
CT: decreased risk of hypothyroidism
TT: normal

AutoImmune Thyroid Gene Variants – Grave’s and Hashimoto’s

A 2012 study published in the Endocrine Journal showed that there are several SNPs in the TSHR gene that influence the risk of the autoimmune thyroid diseases (AITD), which includes Graves’ disease and Hashimoto’s thyroiditis.  The study states that “genetic factors confer 80% contribution to the etiology of AITD”.[ref]  Note that this does not mean that 80% of people with the SNPs have Graves’ or Hashimoto’s.  The prevalence of Hashimoto’s in Caucasian women is between 1 and 2% and is even less in men.[ref] Keep this in mind also when looking at the increased risk – even a 80% increased risk still means the absolute risk of getting Hashimoto’s thyroiditis is still only about 3 in 100.

 

SNP Possible Variants Your Genotype
rs231775 (v.4, v.5) GG: increased risk of Hashimoto’s
AG: increased risk of Hashimoto’s
AA: normal risk of Hasihmoto’s
rs180223 (v.4) TT: increased risk of Hashimoto’s
GT:increased risk of Hashimoto’s
GG: reduced risk of Hashimoto’s [ref]
rs3783938 (v.4) TT: higher frequency of Hashimoto’s (40% increased risk)
CT: higher frequency of Hashimoto’s
CC: normal risk of Hasihmoto’s
rs12101255 (v.4) TT: higher frequency of Graves’ disease (40 – 80% increased risk) [ref]
CT: higher frequency of Graves’ disease
CC: normal risk of Grave’s

Thyroid Hormone Receptors  (THRB, THRA)

SNP Possible Variants Your Genotype
rs28933408 (v.4) TT: thyroid hormone resistance  [ref]
GT: carrier of thyroid hormone resistance mutation
GG: normal

Lifehacks

  • Selenium is essential to the conversion of T4 to T3.  Brazil nuts are a good source of selenium, and supplements are also available.
  • The dietary flavonoid kaempferol, found in apples, onions, leeks, grapes, and other fruits and vegetables, induces DIO2 increasing conversion to T3. [study]
  • There are thyroid glandular supplements (dried thyroid gland) which may — or may not — increase thyroid hormones. The reviews are mixed. It is interesting to note that people historically ate most parts of animals including the thyroid gland.  Sweetbreads are the thyroid glands of calves or lambs.
  • Gluten is often pointed to as a culprit in autoimmune thyroid diseases (Graves and Hashimoto’s).  A 2003 study showed that ~5% of patients with autoimmune thyroiditis also had immune reactions to gluten.[study]  While that isn’t a huge percentage, it may be worth trialing a gluten-free diet if you have an autoimmune thyroid disease.
  • In studies, fasting and critical illnesses increase the levels of DIO3, which is the enzyme that deactivates thyroid hormone.[study]  Avoiding fasting (and illness!) should thus be better for thyroid hormone supply.
  • Light and circadian rhythms play a role in DIO3 expression as well.[study] Blocking blue light in the evening (from LED bulbs, TV screens, etc) by wearing blue-blocking glasses will help to keep your circadian rhythm on track.
  • Several recent studies have also pointed to the hereditary epigenetic effects on DIO3 as well.  [study]
  • For autoimmune thyroid problems, myo-inositol and selenium have been shown to reduce antibody levels. [study]
  • Vitamin D supplement has been shown to reduce Hashimoto’s antibody levels. [study]  This is the one that I use that has coconut oil instead of soybean oil.  (Not saying that anyone should by the brand because I use it — rather that you should make sure that read the ingredients so that you don’t end up with soybean oil or cottonseed oil.)

Recent studies on thyroid levels and chemical toxins:
With so many people having problems with thyroid hormone levels, the question becomes:  Why now? What is causing this explosion? The foods that we are eating and the fact that we no longer eat the thyroid glands of animals probably plays a role in the hypothyroid epidemic. Additionally, chemicals that are found in nearly everyone’s bloodstream, such as PFOA’s, BPA and phthalates, have been shown in several recent studies to be related to lower thyroid levels.  Study results include:

  • PFAS (Perfluoroalkyl substances in cleaners, insecticides, flame retardants, carpet and fabric stain repellant, and food packaging) affect TSH levels [study]
  • BPA and phthalates (in plastics and register receipts) affect thyroid levels.[study] Read more about how genes play a role in your ability to detox BPA and phthalates.
  • Triclosan (previously used in antibacterial soaps) affects T3 and T4 levels as well as other markers. [study]
  • Depending on your DIO2 genes, organochlorides (in pesticides) may make a significant difference in your thyroid levels.[study]
  • Sucralose (Splenda) also alters thyroid hormone levels by increasing rT3 (a rat study) [study]