Genetic Factors That Might Lead to Different Responses in Individuals Exposed to Perchlorate Franco Scinicariello, H. Edward Murray, Lester Smith, Sharon Wilbur, and Bruce A. Fowler Division of Toxicology, Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention, Atlanta, Georgia, USA 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. Key words: genetic susceptibility, hypothyroidism, mutations, NIS, Pendred syndrome, pendrin, perchlorate, thyroid gland, TPO. Environ Health Perspect 113:1479-1484 (2005) . doi:10.1289/ehp.8076 available via http://dx.doi.org/ [Online 29 June 200] Address correspondence to F. Scinicariello, Division of Toxicology, ATSDR, CDC, 4770 Buford Highway, MS: F-32, Atlanta, GA 30341 USA. Telephone: (770) 488-3331. Fax: (770) 488-4178. E-mail: fes6@cdc.gov We thank O. Harris for critical comments. This project was supported under a cooperative agreement from the Centers for Disease Control and Prevention through the Association of Teachers of Preventive Medicine (ATPM) . F.S. is a recipient of an ATPM Career Development Award. The authors declare they have no competing financial interests. Received 2 March 2005 ; accepted 29 June 2005. The full version of this article is available for free in HTML or PDF formats. |