Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 OC5.8

SFEBES2009 Oral Communications Steroids and thyroid (8 abstracts)

The effect of genetic variation in PDE8B and DIO1 on thyroid hormone levels

Peter Taylor 1 , Vijay Panicker 1, , Ahmed Iqbal 1 , Nicholas Timpson 3 , John Walsh 2 & Colin Dayan 1


1Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, University of Bristol, Bristol, UK; 2School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia; 3Department of Social Medicine, MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.


Background: Single-nucleotide polymorphisms (SNPs) allow us to study effects of genetic variation on thyroid hormone levels. Phosphodiesterase 8B (PDE8B) is a protein responsible for cAMP generation, found in thyroid and brain tissue, but not normal pituitary tissue. Variation at this locus has been reported to influence TSH levels, but its effect on T3 and T4 had not been studied in the general population. Deiodinase 1 (DIO1) is known to influence T4 and T3/T4 ratio, but not TSH levels. We examined the effect of SNPs rs4704397 (PDE8B) and rs2235544 (DIO1) on serum thyroid hormone levels.

Methods: We studied 917 patients with thyroid hormone levels in the reference range. Thyroid function was measured on two occasions in 1981 and 1995 from the Busselton Health Study (T3 not measured in 1981).

Results: TSH varied by PDE8B genotype, highest in the AA genotype P=7.08×10−6 (1981) P=8.03×10−6 (1995) causing a TSH rise equal to 0.26 S.D. Variation in PDE8B had no effect on serum T3 and T4 concentrations. Variation in DIO1 genotype had no effect on TSH but affected T4 levels, P=0.016 (1981) and P=0.001 (1995), with greatest effect seen on T3/T4 ratio P=5.93×10−4 (1995).

Conclusion: We confirmed the effect of PDE8B on TSH and DIO1 on serum T4 and serum T3/T4 ratio. Surprisingly there was no effect of PDE8B on T3 and T4 levels. Rather than influencing intrinsic thyroid hormone production variation in PDE8B appears to alter an individual’s ‘set point’ for TSH. There is no effect of DIO1 variation on TSH levels implying that the alteration in T4 and T3/T4 ratio is perceived by the brain as ‘neutral.’ This study highlights that common genetic variation can affect different aspects of the thyroid hormone pathway, independently from each other.

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