Type 2 Deiodinase A/G (Thr92Ala) Polymorphism and Circulating Thyroid Hormone Level of Childbearing Age Women in Area Replete with Iodine Deficiency Disorders

Authors

  • Agus Wibowo National Institute Health Research and Development Station of Magelang, Indonesia Ministry of Health, Magelang, Indonesia
  • Taufiq Hidayat National Research and Innovation Agency, Cibinong Science Center, Bogor, Indonesia
  • Sri Nuryani Wahyuningrum National Institute Health Research and Development Station of Magelang, Indonesia Ministry of Health, Magelang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.11017

Keywords:

Polymorphism, Thr92Ala, TSH, Thyroid hormone, Iodothyronine deiodinase

Abstract

BACKGROUND: Iodothyronine deiodinase (DIO) is an enzyme that regulates thyroid hormone activity. DIO consists of three types: deiodinase 1 (D1), 2 (D2), and 3 (D3). D2 is a gene that plays an important role in regulation of the biochemistry of the thyroid hormone in several tissues. D2 also plays a role in the production of triiodothyronine and controlling thyroid hormone signals. This study measured the observation that about 15% of the normal population show that D2 gene polymorphism (Thr92Ala) potentially affects the activity of D2.

AIM: This study aimed to determine D2 polymorphisms and their association with thyroid hormone levels in women of childbearing age in replete iodine deficiency disorder areas.

METHODS: Total number of subjects was 131. Analysis of serum TSH, T3, fT3, T4, and fT4 levels was done using ELISA. Polymorphism of Thr92Ala was analyzed by PCR-RFLP method.

RESULTS: The results showed that the frequencies of the genotypes Thr92Ala were AA 16.79%, AG 41.22%, and GG 41.99%, whereas the allele frequency A 37.5% and G 62.5% (p HWE = 0.171). In this study, we found no differences of TSH and thyroid hormone level between group of each allel. Mean of TSH and thyroid hormone level was on normal range.

CONCLUSION: This D2 polymorphism is associated with fTlevels rather than fTbut not statistically significant. Heterozygous alleles at D2 AG have higher TSH levels compared with homozygous alleles.

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References

Bochukova E, Schoenmakers N, Agostini M, Schoenmakers E, Rajanayagam O, Keogh JM, et al. A mutation in the thyroid hormone receptor alpha gene. N Engl J Med. 2012;366(3):243-9. https://doi.org/10.1056/NEJMoa1110296 PMid:22168587 DOI: https://doi.org/10.1056/NEJMoa1110296

Peeters RP, van Toor H, Klootwijk W, de Rijke YB, Kuiper GG, Uitterlinden AG, et al. Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab. 2003;88(6):2880-8. https://doi.org/10.1210/jc.2002-021592 PMid:12788902 DOI: https://doi.org/10.1210/jc.2002-021592

Bianco AC, Kim BW. Deiodinases : Implications of the local control of thyroid hormone action. J Clin Invest. 2006;116(10):2571-9. https://doi.org/10.1172/JCI29812 PMid:17016550 DOI: https://doi.org/10.1172/JCI29812

Bianco AC, Salvatore D, Gereben ZS, Berry MJ, Larsen PR. Biochemistry, Cellular and Molecular Biology , and Physiological Roles of the Iodothyronine. Endocr Rev. 2018;23(1):38–89. http://dio.org/10.1210/edrv.23.1.0455 PMid:11844744 DOI: https://doi.org/10.1210/edrv.23.1.0455

Panicker V. Genetics of thyroid function and disease. Clin Biochem Rev. 2011;32(4):165-75. PMid:22147956

Peeters RP, van den Beld AW, Attalki H, van Toor H, De Rijke YB, Kuiper GG, et al. A new polymorphism in the Type II deiodinase gene is associated with circulating thyroid hormone parameters. Am J Physiol Endocrinol Metab. 2005;289(1):E75-81. https://doi.org/10.1152/ajpendo.00571.2004 PMid:15727947 DOI: https://doi.org/10.1152/ajpendo.00571.2004

Bianco AC, Casula S. Thyroid hormone replacement therapy: Three simple questions, complex answers. Eur Thyroid J. 2012;1(2):88-98. https://doi.org/10.1159/000339447 PMid:24783002 DOI: https://doi.org/10.1159/000339447

Dora JM, Machado WE, Rheinheimer J, Crispim D, Maia AL. Association of the Type 2 deiodinase Thr92Ala polymorphism with Type 2 diabetes: Case-control study and meta-analysis. Eur J Endocrinol. 2010;163(3):427-34. https://doi.org/10.1530/EJE-10-0419 PMid:20566590 DOI: https://doi.org/10.1530/EJE-10-0419

Dora JM, Wajner SM, Estivalet AA, Crispim D, Maia AL, Leiria LB. The rs225017 polymorphism in the 3‘UTR of the human DIO2 gene is associated with increased insulin resistance. PLoS One. 2014;9(8):e103960. https://doi.org/10.1371/journal.pone.0103960 PMid:25105294 DOI: https://doi.org/10.1371/journal.pone.0103960

Mcaninch EA, Bianco AC. Thyroid Disorders Editorial the Thr92AlaD2 Polymorphism May Play a Novel Role in Hypothyroidism. Vol. 34. Thyroid Disorders Editorial; 2015. DOI: https://doi.org/10.17925/USE.2015.11.02.92

Loos C, Moeller K, Fröhlich F, Hucho T, Hasenauer J. A hierarchical, data-driven approach to modeling single-cell populations predicts latent causes of cell-to-cell variability. Cell Syst. 2018;6(5):593-603.e13. https://doi.org/10.1016/j.cels.2018.04.008 DOI: https://doi.org/10.1016/j.cels.2018.04.008

Campos-Barros A, Amma LL, Faris JS, Shailam R, Kelley MW, Forrest D. Type 2 iodothyronine deiodinase expression in the cochlea before the onset of hearing. Proc Natl Acad Sci U S A. 2000;97(3):1287-92. https://doi.org/10.1073/pnas.97.3.1287 PMid:10655523 DOI: https://doi.org/10.1073/pnas.97.3.1287

Hall JA, Ribich S, Christoffolete MA, Simovic G, Correa- Medina M, Patti ME, et al. Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. Endocrinology. 2010;151:4573-82. https://doi.org/10.1210/en.2010-0511 PMid:20660060 DOI: https://doi.org/10.1210/en.2010-0511

De Jesus LA, Carvalho SD, Ribeiro MO, Schneider M, Kim SW, Harney JW, et al. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest. 2001;108(9):1379-85. https://doi.org/10.1172/JCI13803 PMid:11696583 DOI: https://doi.org/10.1172/JCI200113803

Bassett JH, Boyde A, Howell PG, Bassett RH, Galliford TM, Archanco M, et al. Optimal bone strength and mineralization requires the Type 2 iodothyronine deiodinase in osteoblasts. Proc Natl Acad Sci U S A. 2010;107(16):7604-9. https://doi.org/10.1073/pnas.0911346107 PMid:20368437 DOI: https://doi.org/10.1073/pnas.0911346107

Dentice M, Marsili A, Ambrosio R, Guardiola O, Sibilio A, Paik JH, et al. The FoxO3/Type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. J Clin Invest. 2010;120(11):4021-30. https://doi.org/10.1172/JCI43670 PMid:20978344 DOI: https://doi.org/10.1172/JCI43670

Freitas BC, Gereben B, Castillo M, Kalló I, Zeöld A, Egri P, et al. Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells. J Clin Invest. 2010;120(6):2206-17. https://doi.org/10.1172/JCI41977 PMid:20458138 DOI: https://doi.org/10.1172/JCI41977

Karki R, Pandya D, Elston RC, Ferlini C. Defining “mutation” and “polymorphism” in the era of personal genomics. BMC Med Genomics. 2015;8(37):1-7. Available from: https://doi.org/10.1186/s12920-015-0115-z DOI: https://doi.org/10.1186/s12920-015-0115-z

Widodo US. Results of Analysis of UIE Examination in Kulon Progo Regency. Final Research Report. BP2GAKI; 2007.

Theodoropoulou A, Vagenakis AG, Makri M, Markou KB. Thyroid hormone synthesis and secretion in humans after 80 milligrams of iodine for 15 days and subsequent withdrawal. J Clin Endocrinol Metab. 2007;92(1):212-4. https://doi.org/10.1210/jc.2006-1189 PMid:17047024 DOI: https://doi.org/10.1210/jc.2006-1189

Bianco AC, Kim BS. Pathophysiological relevance of deiodinase polymorphism. Curr Opin Endocrinol Diabetes Obes. 2018;25(5):341-6. https://doi.org/10.1097/MED.0000000000000428 PMid:30063552 DOI: https://doi.org/10.1097/MED.0000000000000428

Hashemipour M, Amini M, Aminorroaya A, Dastjerdi ML, Rezvanian H, Kachoei A, et al. High prevalence of goiter in an iodine replete area: Do thyroid auto-antibodies play a role ? Asia Pac J Clin Nutr. 2007;16(3):403-10. PMid:17704020

Trent RJ. Omics.In: Trent RJ, editor. Molecular Medicine 4th ed. Boston/Waltham: Academic Press; 2012. p. 117–52. Available from https://www.sciencedirect.com/science/article/pii/B9780123814517000049 DOI: https://doi.org/10.1016/B978-0-12-381451-7.00004-9

Peeters RP, van der Deure WM, Visser TJ. Genetic variation in thyroid hormone pathway genes ; polymorphisms in the TSH receptor and the iodothyronine deiodinases. Eur J Endocrinol. 2006;155(5):655-62. https://doi.org/10.1530/eje.1.02279 PMid:17062880 DOI: https://doi.org/10.1530/eje.1.02279

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Published

2022-11-27

How to Cite

1.
Wibowo A, Hidayat T, Wahyuningrum SN. Type 2 Deiodinase A/G (Thr92Ala) Polymorphism and Circulating Thyroid Hormone Level of Childbearing Age Women in Area Replete with Iodine Deficiency Disorders. Open Access Maced J Med Sci [Internet]. 2022 Nov. 27 [cited 2024 Apr. 19];10(A):1653-7. Available from: https://oamjms.eu/index.php/mjms/article/view/11017

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