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.

Association of SLC26A4 muations with clinical features and thyroid function in deaf infants with enlarged vestibular aqueduct

“…Pendred syndrome is clinically differentiated from NSRD with EVA by the presence of goiter. Variability of the goiter due to other genetic and/or environmental factors has been reported (Yang et al 2005;Scinicariello et al 2005). When goiter is found in Pendred syndrome, it is most often euthyroidal and not evident until the second decade of life.…”

“…As a result, thyroglobulin is stored at high concentrations in the thyroid follicular lumen. Adequate nutritional iodide intake from vegetable and dairy food products (Scinicariello et al 2005) may compensate for an iodide transport deficit, thereby maintaining the euthyroid status. In conclusion, we speculate that serum thyroglobulin level is elevated by an abnormal iodide-trapping mechanism caused by pendrin dysfunction during infancy and that thyroid function can be rescued by some genetic (Royaux et al 2000;Dentice et al 2005) or environmental cofactors, such as nutritionally supplied iodide, after the age of 10 years.…”

Perchlorate in the United States. Analysis of Relative Source Contributions to the Food Chain

“…Although a National Academy of Sciences panel (12) has provided a reference safe dose for perchlorate, a general consensus on what constitutes a safe dose for infants, children, or other more sensitive segments of the population will likely continue to be debated for some time to come (13)(14)(15)(16)(17)(18)(19). Unfortunately, it is often forgotten in the perchlorate debate that the key issue is iodine nutrition.…”

Risks for public health related to the presence of chlorate in food

“…However, no data are available to support this hypothesis. These life stages are identified as being particularly sensitive to inhibition of thyroid iodine uptake, because they do not have the reserve capacity existing in adult humans (Zoeller, 2003;Scinicariello et al, 2005;Ginsberg et al, 2007).…”