SFEBES2014 Oral Communications Young Endocrinologists prize session (6 abstracts)
The Thr92Ala substitution in deiodonase-2 is associated with increased odds of a sub-optimal IQ score in children with low-normal thyroid function
Peter Taylor 1,2 , Onyebuchi Okosieme 1 , Adrian Sayers 2 , Kate Northstone 2 , Mohd Draman 1 , Kirsty Stevenson 3 , Wolf Woltersdorf 3 , Andrew Taylor 4 , Elizabeth Pearce 5 , Vijay Panicker 6 , Marian Ludgate 1 , John Gregory 1 , John Lazarus 1 , Nicholas Timpson 2 , Sue Channon 6 & Colin Dayan 1
1Cardiff University, Cardiff, UK; 2University of Bristol, Bristol, UK; 3Bristol Royal Infirmary University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 4Royal United Hospital, Bath, UK; 5Boston University, Boston, Massachusetts, USA; 6St David’s Children’s Centre, Cardiff, UK.
Importance: Thyroid hormone is essential for cognitive development. The Thr92Ala substitution in deiodonase-2 appears to reduce intracellular availability of active thyroid hormone. Individuals with low-normal serum thyroid hormone levels and this substitution might have insufficient intracellular thyroid hormone for optimal cognitive development.
Objective: To explore whether individuals with low thyroid hormone bioavailability – free thyroxine in the lowest quartile and homozygous for the Thr92Ala substitution in deiodonase-2 – had higher odds of an IQ <85.
Design: Population based cohort study
Participants and setting: 3123 individuals with genetic data, thyroid function (at age 7) and cognitive assessments (at age 8) available in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children.
Main outcome measures: The odds of having an IQ score ≤85 in children with low thyroid hormone bioavailability compared to the rest of the study population. Analyses were adjusted for age, gender, ethnicity, thyroid hormone parameters, markers of social class and early life environment.
Results: Children with low thyroid hormone bioavailability had higher odds of a total IQ score <85 (OR=4.15, 95% CI 1.60, 10.8, P=0.003) and a lower mean IQ (P=0.003) compared to individuals with free thyroxine above the lowest quartile not homozygous for the Thr92Ala substitution. There was no evidence of association with IQ in individuals with free thyroxine in the lowest quartile, or with the Thr92Ala substitution alone; however we observed evidence of interaction between free thyroxine in the lowest quartile and the Thr92Ala substitution in their relationship with IQ (P=0.008).
Conclusions: Common genetic variation in the intracellular thyroid hormone pathway appears to substantially modify the effect of low-normal serum thyroid hormone levels on IQ. This highlights the importance of the intracellular pathway in determining an individual’s thyroid status and raises the possibility that levothyroxine supplementation in a genotype dependent manner to children with lower thyroid hormone levels may improve cognitive outcomes.
Volume 34
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Endocrine Abstracts
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