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1 Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: r.peeters{at}erasmusmc.nl.
Introduction: D2 is important in the regulation of local thyroid hormone bioactivity in certain tissues. D2 in skeletal muscle may also play a role in serum T3 production. In this study we identified a polymorphism in the 5'-UTR of the D2 gene (D2-ORFa-Gly3Asp). We investigated the association of D2-ORFa-Gly3Asp, and of the previously identified D2- Thr92Ala polymorphism, with serum iodothyronine levels. Methods: D2-ORFa-Gly3Asp was identified by sequencing the 5'-UTR of 15 randomly selected individuals. Genotypes for D2-ORFa-Gly3Asp were determined in 156 healthy blood donors (age 46.3±12.2) and 350 ambulant elderly men (age 77.7±3.5) and related to serum iodothyronine and TSH levels. Results: D2-ORFa-Asp3 had an allele frequency of 33.9% in blood bank donors and was associated with serum T4 (Gly/Gly vs Gly/Asp vs Asp/Asp = 7.06±0.14 vs 6.74±0.15 vs 6.29±0.27 µg/dl, P=0.01), FT4 (1.22±0.02 vs 1.16±0.02 vs 1.06±0.04 ng/dl, P=0.001), rT3 (P=0.01) and T3/T4 (P=0.002) in a dose-dependent manner, but not with serum T3 (P=0.59). In elderly men, D2-ORFa-Asp3 had a similar frequency but was not associated with serum iodothyronine levels. Conclusion: This new polymorphism in the 5'-UTR of D2 is associated with iodothyronine levels in blood donors, but not in elderly men. We hypothesize that this might be explained by the decline in skeletal muscle size during aging, resulting in a relative decrease in the contribution of D2 to serum T3 production.
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