DIO1
| is a | gene |
| is | mentioned by |
| Full name | iodothyronine deiodinase 1 |
| EntrezGene | 1733 |
| PheGenI | 1733 |
| VariationViewer | 1733 |
| ClinVar | DIO1 |
| GeneCards | DIO1 |
| dbSNP | 1733 |
| Diseases | DIO1 |
| SADR | 1733 |
| HugeNav | 1733 |
| wikipedia | DIO1 |
| DIO1 | |
| gopubmed | DIO1 |
| EVS | DIO1 |
| HEFalMp | DIO1 |
| MyGene2 | DIO1 |
| 23andMe | DIO1 |
| UniProt | P49895 |
| OMIM | 147892 |
| # SNPs | 3 |
| Max Magnitude | Chromosome position | Summary | |
|---|---|---|---|
| rs11206244 | 1.1 | 53,910,028 | |
| rs12095080 | 1 | 53,911,057 | |
| rs2235544 | 2 | 53,909,897 |
According to NCBI Gene: "The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the activation, as well as the inactivation of thyroid hormone by outer and inner ring deiodination, respectively. The activation reaction involves the conversion of the prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4), secreted by the thyroid gland, to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by 5'-deiodination."
[PMID 25040645
] A 2014 article called "Defending plasma T3 is a biological priority" explained the role of D1, the enzyme produced by the DIO1 gene: Healthy adults produce "about 30 µg T3/day), of which about 5 µg are secreted directly from the thyroid." The vast bulk of T3, the active form of the thyroid hormone, is produced outside of the thyroid by means of deiodination of T4 to T3. "There are two deiodinase pathways that lead to extrathyroidal T3 production, the type 1 deiodinase (D1) and D2 pathways. In turn, the third deiodinase pathway (type 3 deiodinase, aka D3) is involved in catabolism of both T4 and T3, terminating thyroid hormone action." "In a healthy adult individual, D2 is thought to mediate the bulk of T3 production, approximately 20 µg/day, with a minor contribution provided by D1 (5 µg/day)." While D2 is active in most tissues and organs in varying amounts, "D1 expression is restricted to the liver and kidney."
[PMID 18815314] Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. This 2008 review explained
- D1 activity is reduced in hypothyroidism, and increased in hyperthyroidism. DIO1 polymorphisms, namely "D1a-C/T at position 785 (GI 4557521; rs11206244), and D1b-A/G at position 1814 (rs12095080)," can impair D1 expression; studies have shown reduced serum T3 levels in individuals with this haplotype after their fourth decade of life.
- D1 is also impaired in "nonthyroidal illness syndrome," or "consumptive hypothyroidism," a syndrome present "in about 75% of hospitalized patients," when deiodinase pathways are abnormal, resulting in a fall in serum T3 and a rise in serum rT3 (reverse T3). The authors admit that it was controversial at the time of writing (2008) whether this low T3 high rT3 state was an adaptive mechanism or pathological, but it was known that D1 activity is impaired by cytokines induced in illness. In addition, IL-1 and IL-6 inhibit induction of D1 in the liver. However, impaired D1 activity is not the only contributor to nonthyroidal illness; increased D3 activity is responsible for converting T4 into reverse T3 (rT3). Normally, D1 catabolizes rT3 into inactive form, but in nonthyroidal illness, lower D1 activity prevents the clearance of rT3. The increased expression of D3 deiodinase also catabolizes more T3, which can lower T3 levels, thus contributing to the state of hypothyroidism and reduced D1 activity.
[PMID 21563302] A 2012 study "The Relationship of Deiodinase 1 Genotype and Thyroid Function to Lifetime History of Major Depression in Three Independent Populations," researchers "confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3’ UTR of DIO1 (rs11206244), were associated with altered free thyroxine (FT4) levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD (Major Depression) in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD." (Abstract)
[PMID 25944909] A 2015 study "Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome (NTIS) Associated with Hepatocellular Carcinoma (HCC)" explained that "Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3′-triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with malignancy. Decreased activity of type I 5′-deiodinase (DIO1), which converts T4 to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which heterodimerizes with retinoid X receptor (RXR) and regulates transcription of target genes, such as DIO1."
[PMID 26947333] Published 2016: "Type 1 5'-deiodinase activity is inhibited by oxidative stress and restored by alpha-lipoic acid in HepG2 cells." Results: "Alpha-lipoic acid (LA) treatment notably restored DIO1 activity, T3 and rT3 level, as well as transcriptional abnormalities of inflammation-associated genes. It suggests that oxidative stress may reduce DIO1 activity by an indirect way like activating cellular inflammatory responses. All these results indicate that the oxidative stress downregulates the conversion of T4 to T3 through DIO1 function in HepG2 cells." (Abstract)
[PMID 21912701] A 2011 study "MiR-224 Targets the 3′UTR of Type 1 5′-Iodothyronine Deiodinase Possibly Contributing to Tissue Hypothyroidism in Renal Cancer" found that "Tumor specific changes in expression of miR-224 negatively correlated with changes in DIO1 expression and intracellular T3 concentration" (Abstract).
[PMID 24910925] Published 2014: "Effect of UGT1A1, UGT1A3, DIO1 and DIO2 polymorphisms on L-thyroxine doses required for TSH suppression in patients with differentiated thyroid cancer." Results: "The association of T4 dose with UGT1A haplotype is attributed to reduced UGT1A1 expression and T4 glucuronidation in liver of carriers of low expression UGT1A1 rs8175347 alleles," however, UGT1A1 only influenced levels by 2%. "The DIO1 and DIO2 genotypes had no influence of T4 dosage." (Abstract)
[PMID 14657345] In a 2016 article "Type 1 Deiodinase Regulates ApoA-I Gene Expression and ApoA-I Synthesis Independent of Thyroid Hormone Signaling," researchers endeavoured to understand why "Plasma levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) are reduced in individuals with defective insulin signaling." Results: "Reductions in DIO1 expression reduce the expression of ApoA-I in a 3,5,3'-triiodothyronine-/thyroid hormone response element-independent manner." (Abstract)
