title: 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.
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Center, Leiden, The NetherlandsDepartment of General Internal MedicineRadboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The NetherlandsDepartment of EndocrinologyErasmus University Medical Center, Rotterdam, The NetherlandsWalaeus Medical LibraryLeiden University Medical Center, Leiden, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Verloop
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Center, Leiden, The NetherlandsDepartment of General Internal MedicineRadboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The NetherlandsDepartment of EndocrinologyErasmus University Medical Center, Rotterdam, The NetherlandsWalaeus Medical LibraryLeiden University Medical Center, Leiden, The Netherlands.
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Center, Leiden, The NetherlandsDepartment of General Internal MedicineRadboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The NetherlandsDepartment of EndocrinologyErasmus University Medical Center, Rotterdam, The NetherlandsWalaeus Medical LibraryLeiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Center, Leiden, The NetherlandsDepartment of General Internal MedicineRadboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The NetherlandsDepartment of EndocrinologyErasmus University Medical Center, Rotterdam, The NetherlandsWalaeus Medical LibraryLeiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Schoones
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Center, Leiden, The NetherlandsDepartment of General Internal MedicineRadboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The NetherlandsDepartment of EndocrinologyErasmus University Medical Center, Rotterdam, The NetherlandsWalaeus Medical LibraryLeiden University Medical Center, Leiden, The NetherlandsDepartments of EndocrinologyClinical EpidemiologyLeiden University Medical Center, Leiden, The NetherlandsDepartment of General Internal MedicineRadboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The NetherlandsDepartment of EndocrinologyErasmus University Medical Center, Rotterdam, The NetherlandsWalaeus Medical LibraryLeiden University Medical Center, Leiden, The Netherlands J.Smit@aig.umcn.nl.
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
mesh_terms: D000818:Animals; D004704:Endocrinology / Q000379:methods / Q000639:trends; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics*; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007334:Insulin-Like Growth Factor I; D007453:Iodide Peroxidase; D000097564:Iodothyronine Deiodinase Type II; C583557:IGF1 protein, human; C109812:iodothyronine deiodinase type I