GENETICS IN ENDOCRINOLOGY: Genetic variation in deiodinases: a systematic review of potential clinical effects in humans

Abstract

Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation.

Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function

“…We found an inverse correlation between TSH-standardized T4 production and T4–T3 conversion across the euthyroid reference range (71). This contradicts the assumption that variation between thyroid hormones and TSH may be randomly defined in euthyroid subjects by genetic variation in the formation of set points (72–74), rather indicating early homeostatic control across the euthyroid spectrum (71). The euthyroid reference range for FT3 becomes dependent on a progressive alteration in the controlling interplay between TSH, FT4, and FT3 across the range.…”

Serum free thyroxine levels are associated with the efficacy of weight reduction therapy in obese female patients

“…However, so far, no effect of D1 polymorphisms on BMI was found in a cohort of healthy elderly men [22,23].…”

Incidence of total hip or knee replacement due to osteoarthritis in relation to thyroid function: a prospective cohort study (The Nord-Trøndelag Health Study)

“…There has been an increased interest in the effect of deiodinase polymorphisms on osteoarthritis [5]. Iodothyronine deiodinases represent a family of proteins involved in local homeostasis of thyroxine (T4) and triiodothyronine (T3).…”

“…Thyroid hormones play a role in the remodelling and maintenance of bone, and recent studies also indicate the potential importance of thyroid hormones in joints and articular cartilage [4]. Genetic studies have suggested that deiodinase-regulated local availability of the active thyroid hormone triiodothyronine (T3) plays an important role in cartilage maintenance and repair [5]. Further data have indicated that increased intracellular T3 availability increases the risk of osteoarthritis, leading to the hypothesis that reduced tissue T3 availability protects joints from development of osteoarthritis [6].…”