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Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases

Department of Internal Medicine, Erasmus University Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands

(Correspondence should be addressed to R P Peeters; Email: r.peeters{at}erasmusmc.nl)

Serum thyroid parameters show substantial inter-individual variability, in which genetic variation is a major factor. Findings in patients with subclinical hyper- and hypothyroidism illustrate that even minor alterations in serum thyroid function tests can have important consequences for a variety of thyroid hormone-related clinical endpoints, such as atherosclerosis, bone mineral density, obesity, and heart rate. In the last few years, several studies described polymorphisms in thyroid hormone pathway genes that alter serum thyroid function tests. In this review, we discuss the genetic variation in the TSH receptor and iodothyronine deiodinases. We discuss the possible consequences of these studies for the individual patient and also the new insights in thyroid hormone action that can be obtained from these data.