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.