title: Genetic factors that might lead to different responses in individuals exposed to perchlorate.
abstract: Perchlorate has been detected in groundwater in many parts of the United States, and recent detection in vegetable and dairy food products indicates that contamination by perchlorate is more widespread than previously thought. Perchlorate is a competitive inhibitor of the sodium iodide symporter, the thyroid cell-surface protein responsible for transporting iodide from the plasma into the thyroid. An estimated 4.3% of the U.S. population is subclinically hypothyroid, and 6.9% of pregnant women may have low iodine intake. Congenital hypothyroidism affects 1 in 3,000 to 1 in 4,000 infants, and 15% of these cases have been attributed to genetic defects. Our objective in this review is to identify genetic biomarkers that would help define subpopulations sensitive to environmental perchlorate exposure. We review the literature to identify genetic defects involved in the iodination process of the thyroid hormone synthesis, particularly defects in iodide transport from circulation into the thyroid cell, defects in iodide transport from the thyroid cell to the follicular lumen (Pendred syndrome), and defects of iodide organification. Furthermore, we summarize relevant studies of perchlorate in humans. Because of perchlorate inhibition of iodide uptake, it is biologically plausible that chronic ingestion of perchlorate through contaminated sources may cause some degree of iodine discharge in populations that are genetically susceptible to defects in the iodination process of the thyroid hormone synthesis, thus deteriorating their conditions. We conclude that future studies linking human disease and environmental perchlorate exposure should consider the genetic makeup of the participants, actual perchlorate exposure levels, and individual iodine intake/excretion levels.
authors.affiliation: Division of Toxicology, Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. fes6@cdc.gov
authors.forename: Franco
authors.initials: F
authors.lastname: Scinicariello
authors.forename: H Edward
authors.initials: HE
authors.lastname: Murray
authors.forename: Lester
authors.initials: L
authors.lastname: Smith
authors.forename: Sharon
authors.initials: S
authors.lastname: Wilbur
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Fowler
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D007455:Iodine / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D010472:Perchlorates / Q000633:toxicity*; D027981:Symporters / Q000037:antagonists & inhibitors; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D001324:Autoantigens; D015415:Biomarkers; D004785:Environmental Pollutants; D007453:Iodide Peroxidase; D007454:Iodides; D007455:Iodine; D033862:Iron-Binding Proteins; D010472:Perchlorates; D027981:Symporters; D013963:Thyroid Hormones; D000099209:Sodium-Iodide Symporters; C056658:TPO protein, human