The thyroid is a master regulator of many of your body’s systems. It is integrally involved in metabolism and helps maintain body temperature, heart rate, breathing, and body weight. The thyroid is a butterfly-shaped gland that is located at the front of your throat (right below the Adam’s apple for men). [ref]
Your genes play a big role in how well your thyroid works and how your body produces and converts the different forms of thyroid hormone.
More people than ever are having problems with low thyroid levels. In 2016, the #1 prescribed drug in the US was Synthroid, a synthetic thyroid hormone with 123 million people on the drug.[ref] Thyroid hormone levels play a vital role in how you feel and in your overall good health.
If you have thyroid problems, learning which genetic variants you carry may be a way to shed some light on what is going on with your thyroid. Knowing where your genetic susceptibilities are can lead to figuring out (with your doctor) the best way to solve the problem. YOU are your own best advocate. I encourage you to learn everything you can about your thyroid health.
The thyroid gland is located in the neck and uses iodine to create the thyroid hormones thyroxine(T4) and triiodothyronine(T3). The rate at which the thyroid gland produces and releases thyroid hormone is controlled by the hypothalamus and the pituitary gland through thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH).
Hypothyroidism is caused by too little thyroid hormone; hyperthyroidism is caused by too much thyroid hormone.
The active form of the thyroid hormone that your body uses is T3. The thyroid gland produces and releases much more T4 than T3 (around 80% is T4), but enzymes can convert T4 to T3 in your tissues and organs. Too much of the active T3 in cells will cause enzymes to inactivate it to reverse T3 (rT3).[ref]
Thyroid hormone levels are an intricate balance between the production of T4, conversion to T3, inactivation to rT3, TSH levels, and the feedback loops controlling TRH and TSH.
In addition to diet and environmental toxins, genetics can play a role at many points along the way.
A good source of background information on all things thyroid is the website (and book) Stop the Thyroid Madness. If you are unfamiliar with the ins-and-outs of thyroid hormones, I recommend that you start there.
The first thing that most doctors check on a blood test is the TSH (thyroid stimulating hormone) level. A person can be naturally slightly higher or lower than average for TSH levels based on their genes. An interesting study published in the journal of the European Society of Endocrinology looked at the heritability of thyroid hormone levels in men who had no thyroid auto-immune disease or dysfunction and found several SNPs that were responsible for approximately 50 – 90% of thyroid hormone variability. Thus TSH levels naturally vary a bit from person to person.
Thyroid stimulating hormone receptor (TSHR) gene codes for a receptor protein that controls thyroid cell metabolism. [ref] TSH (thyroid stimulating hormone) levels are also tied to genetic variations of the TSHR gene. Grave’s disease is an autoimmune condition that affects about 1% of the population. In Graves’ disease, the body produces antibodies against TSHR.
It is thought that one of the reasons that TSHR genetic variants are a risk factor for Graves’ is because the changes in the TSHR gene could cause a slightly different structure for the receptor protein and possibly “exacerbate autoimmune response against TSHR in” Graves’ disease. [ref]
Check your genetic data for rs1991517 D727E (23andMe v.4; AncestryDNA):
Check your genetic data for rs179247 (23andMe v4; AncestryDNA):
Check your genetic data for rs12101255 (23andMe v4;AncestryDNA);
The PDE8B gene variant has been repeatedly associated with TSH levels, specifically in those of European descent.[ref]
Check your genetic data for rs4704397 (23andMe v.4, v.5; AncestryDNA):
Check your genetic data for rs6885099 (23andMe v.4, v.5; AncestryDNA)
The FOXE1 gene (thyroid specific forkhead transcription factor) has also been identified to increase the risk of primary hypothyroidism[ref] and with changes in TSH levels.
Check your genetic data for rs7850258 (23andMe v.4, v.5; AncestryDNA):
Check your genetic data for rs965513 (23andMe v.4, v.5, AncestryDNA):
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]
Check your genetic data for rs3783938 ( 23andMe v.4, AncestryDNA):
Check your genetic data for rs12101255 ( 23andMe v.4, AncestryDNA):
Check your genetic results for rs179247 (23andMe v4, AncestryDNA):
Thyroid peroxidase (TPO) antibodies are a marker of autoimmune thyroid disease. Several genetic variants in the TPO gene are associated with an increased risk of autoimmune thyroid disease.
Check your genetic data for rs2071403 (23andMe v5; AncestryDNA.)
The PTPN22 gene is associated with increased risk of many autoimmune diseases, including Hashimotos.
Check your genetic data for rs2476601 (23andMe v4; AncestryDNA):
The deiodinase 1 (DIO1) gene encodes a protein that converts T4 to T3 and is involved in the degradation of both T3 and T4 in the liver, kidney, thyroid, and pituitary gland. Iodine and selenium are involved in these reactions.[ref] DIO2 is also involved in the conversion of T4 to T3, mainly in the skeletal muscles, central nervous system, pituitary, thyroid, heart, and brown fat.[ref]
Check your 23andMe results for rs2235544 (v.4, v.5):
Check your 23andMe results for rs11206244 (v.4, v.5):
Check your 23andMe results for rs225014 (v.4):
So why would these deiodinase polymorphisms be important? The most common prescription for hypothyroidism is Synthroid, which is T4 only. One reason for not doing well with Synthroid could be that the T4 is not being converted properly to T3 by the deiodinase enzymes… A recent study showed that patients with the rs225014 C/C or C/T genotype preferred a combo of T3 and T4. (Here is the full text of the study to share with your doctor.)
Thyroid Hormone Receptors (THRB, THRA):
The thyroid hormone receptor genes code for the receptor that brings the thyroid hormone into the target cells. Mutations in these genes cause thyroid hormone resistance. Generally, THRB or THRA mutations will cause hypothyroidism that is recognized and diagnosed in infants or children. In other words, the mutations may cause more severe symptoms that affect growth and development.[ref]
Check your 23andMe results for rs28933408 (v.4):
Check your 23andMe results for i5003323 (v.4):
Check your 23andMe results for i5003327 (v.4):
*Note that for anything that is rare or considered pathogenic, you should heed the warnings from 23andMe not to use their data for medical purposes. Their test information could be wrong, and for anything medically important you should probably get a second test from a clinical testing company.
If you are on thyroid medication or under the care of a doctor, please be sure to talk with your doctor about making any changes, including dietary changes, that could affect your thyroid hormone levels.
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:
I encourage everyone who has thyroid problems to read and research more on this issue.
updated and revised 9/10/18