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- W2038936700 abstract "Summary Introduction Genetic factors have a considerable influence on serum thyroid hormone levels. The C785T and A1814G polymorphisms, located in the 3′ untranslated region of the type 1 deiodinase (D1) gene have been associated with serum FT4 and rT3 levels. Objective In healthy Danish twins, we examined the association of these polymorphisms with serum thyroid hormone levels and determined the proportion of genetic influence explained by these variants. We analysed the underlying functional mechanism by performing mRNA stability measurements and analysed the effect of these variants on D1 activity. Methods Serum thyroid measurements and genotypes of the D1‐C785T and D1‐A1814G polymorphisms were determined in 1192 twins. Structural equation modelling was used to determine heritability estimates. Functional analyses were carried out in D1‐transfected JEG3 cells. Results Carriers of the D1‐785T allele had 3·8% higher FT4 and 14·3% higher rT3 levels, resulting in a lower T3/T4 and T3/rT3 ratio and a higher rT3/T4 ratio. This polymorphism explained 0·87% and 1·79%, respectively, of the variation in serum FT4 and rT3. The D1‐A1814G polymorphism was not associated with serum thyroid hormone levels. No differences in D1 mRNA decay rate or D1 activity were observed between wild‐type D1 and the two variants. Conclusion The D1‐C785T polymorphism is consistently and significantly associated with serum thyroid hormone levels. However, the proportion of genetic influence explained by this particular polymorphism is small. No effect of the polymorphism on D1 mRNA decay rate or D1 activity was observed. The underlying functional mechanism needs to be elucidated." @default.
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- W2038936700 date "2009-05-13" @default.
- W2038936700 modified "2023-10-18" @default.
- W2038936700 title "The effect of genetic variation in the type 1 deiodinase gene on the interindividual variation in serum thyroid hormone levels: an investigation in healthy Danish twins" @default.
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- W2038936700 doi "https://doi.org/10.1111/j.1365-2265.2008.03420.x" @default.
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