Phosphodiesterase 8B Gene Polymorphism Is Associated with Subclinical Hypothyroidism in Pregnancy
Abstract
Background Maternal subclinical hypothyroidism is associated with a number of adverse outcomes in pregnancy. The Endocrine Society's recent consensus guidelines have recommended treatment with T(4) for this condition in pregnancy. The single nucleotide polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene has been found to be associated with altered serum TSH concentrations in the general population. We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy. Methods Serum TSH, FT4, FT3, and thyroid peroxidase antibodies (TPOAbs) were measured in 970 pregnant women at 28 wk gestation. rs4704397 genotype was available on 877 subjects. Reference range calculations were based on the TPOAb-negative women. Results TSH, but not FT4, FT3, or TPOAbs, varied with genotype and was highest in those with the AA genotype (median, 2.16, 1.84, and 1.73 mIU/liter for AA, AG, and GG genotypes, respectively; P = 0.0004). A greater proportion of women with the AA genotype had TSH concentrations above 4.21 mIU/liter, the upper limit of the reference range, compared with the AG and GG genotypes (9.6 vs. 3.5%, respectively; P = 0.004). Maternal PDE8B genotype was not associated with offspring birthweight or gestational age at delivery. Conclusion Genetic variation in TSH levels in pregnancy associated with the PDE8B rs4704397 genotype has implications for the number of wo…
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Subsequent studies also reported the association between PDE8B and higher serum TSH, but not between PDE8B and serum free T4 which would have expected to be lower.
“Subsequent studies also reported the association between PDE8B and higher serum TSH, but not between PDE8B and serum free T4 which would have expected to be lower [53,54] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [53]
Cites
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Subclinical Hyperthyroidism and Pregnancy Outcomes
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Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function
Arnaud-Lopez, L., Usala, G., Ceresini, G., Mitchell, B. D., Pilia, M. G., Piras, M. G., Sestu, N., Maschio, A., Busonero, F., Albai, G., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.04.019 · Cited by 139 · see citing works
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2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism
Wiersinga, W. M., Duntas, L., Fadeyev, V., Nygaard, B., & Vanderpump, M. P. J. (2012) · European Thyroid Journal · doi:10.1159/000339444 · Cited by 427 · see citing works
Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism
Wiersinga, W. M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.258 · Cited by 114 · see citing works
Genetic determination of the hypothalamic–pituitary–thyroid axis: where do we stand?
Medici, M., Visser, W. E., Visser, T. J., & Peeters, R. P. (2015) · Endocrine Reviews · doi:10.1210/er.2014-1081 · Cited by 92 · see citing works
Taylor, P. N., Panicker, V., Sayers, A., Shields, B., Iqbal, A., Bremner, A. P., Beilby, J. P., Leedman, P. J., Hattersley, A. T., Vaidya, B., et al. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-0938 · Cited by 41 · see citing works
Self-citationStavreus Evers, A. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00050 · Cited by 36 · see citing works
- Authors
- Shields, B. M., Freathy, R. M., Knight, B. A., Hill, A., Weedon, M. N., Frayling, T. M., Hattersley, A. T., & Vaidya, B.
- Affiliations
- University of Exeter (GB)
- National Health Service (GB)
- Corresponding author
- Vaidya, Bijay
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-11-01
- Volume
- 94
- Issue
- 11
- Pages
- 4608-4612
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1975086606
- Cited by
- 35
- References
- 5
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 5
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- PDE8B, subclinical hypothyroidism, pregnancy, thyroid-stimulating hormone, genetic polymorphism, thyroid peroxidase antibodies, free thyroxine, birth weight, gestational age, levothyroxine therapy
- MeSH terms
- Autoantibodies, Base Sequence, Female, Genotype, Humans, Hypothyroidism, Iodide Peroxidase, Polymorphism, Genetic, Pregnancy, Thyrotropin, Genetic Variation, 3',5'-Cyclic-AMP Phosphodiesterases
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