Protein tyrosine phosphatase non-receptor type 22 C1858T gene polymorphism in children with Down syndrome and autoimmune thyroid diseases
https://doi.org/10.4081/pmc.2023.283
Accepted: 28 December 2022
HTML: 16
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Autoimmune Thyroid Disease (AIT) is a frequent comorbidity in Down Syndrome (DS). Protein Tyrosine Phosphatase Non- Receptor Type 22 C1858T (PTPN-22 C1858T) gene polymorphisms have a role in the progression of AIT. The study on PTPN- 22 C1858T gene polymorphism as the risk factor of AIT in DS children is still limited. This study aims to evaluate PTPN-22 C1858T polymorphism in Indonesian DS children. A cross-sectional study involving 31 DS children with hypothyroidism (19 boys/12 girls) was conducted for ten months from February to November 2020 at Dr. Soetomo General Hospital Surabaya. The PTPN-22 C1858T gene polymorphism was analyzed using Polymerase Chain Reaction-Restriction-Fragment-Length Polymorphism (PCR-RFLP). Anti-Thyroid Peroxidase (Anti- TPO) and Anti-Thyroglobulin (Anti-TG), FT4, T3, and TSH levels were analyzed using Enzyme-Linked-Immunosorbent-Assay (ELISA). The mean age of the subjects was 19.45±17.3 months. The CT variant of PTPN-22 C1858T was observed in all subjects. The mean level of T3, FT4, and TSH were 1.59±0.45 ng/mL, 0.81±0.57 ng/mL, 0.22±0.21 μU/mL, respectively. Around 83.9% of patients suffered from central hypothyroidism, 12.9% from primary hypothyroidism, and 3.2% from subclinical hypothyroidism. The positive anti-TG and anti-TPO were observed in 96.8% and 58.1%, respectively. CT variant was observed in Indonesian DS children who suffered from hypothyroidism.
Al-Biltagi M. Down syndrome from epidemiologic point of view. EC Paediatrics 2015;82-91.
Ariani Y, Soeharso P, Sjarif DR. Genetic & genomic medicine in Indonesia. Molecular Genetics & Genomic Medicine 2017;5:103-9. DOI: https://doi.org/10.1002/mgg3.284
Iughetti L, Predieri B, Buzzi P, et al. Ten-year longitudinal study of thyroid function in children with Down’s syndrome. Horm Res Paediatr 2014; 82:113-21. DOI: https://doi.org/10.1159/000362450
Graber E, Chacko E, Regelmann MO, et al. Down syndrome & thyroid function. In Rapaport R (ed.), Clinic review articles: endocrinology & metabolism clinics of North America: pediatric endocrinology. Philadelphia USA: Elsevier; 2012. DOI: https://doi.org/10.1016/j.ecl.2012.08.008
Iughetti L, Lucaccioni L, Fugetto F, et al. Thyroid function in down syndrome, Expert Review of Endocrinol & Met 2015;10:525-32. DOI: https://doi.org/10.1586/17446651.2015.1063995
NCBI. PTPN-22 protein tyrosine phosphatese non-receptor type 22 [Homo sapiens (human)]. Accessed: 31 Dec 2021. Available from: https://www.ncbi.nlm.nih.gov/gene/26191
Vang T, Miletic AV, Bottini N, Mustelin T. Protein tyrosin phosphatase PTPN-22 in human autoimmunity. Autoimmunity 2007;40: 453-61. DOI: https://doi.org/10.1080/08916930701464897
Burn GL, Svensson L, Sanchez-Blanco C, et al. Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett 2011;585:3689-98. DOI: https://doi.org/10.1016/j.febslet.2011.04.032
World Medical Association. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull World Health Org 2001;79:373-374. DOI: https://doi.org/10.4414/fms.2001.04031
Soghier L. Reference range values for pediatric care. 2nd ed. American Academy of Pediatric; 2019. DOI: https://doi.org/10.1542/9781610022811
Wu H, Wan S, Qu M, et al. The Relationship between PTPN-22 R620W polymorphisms & the susceptibility to autoimmune thyroid diseases: an updated meta-analysis. Imm Invest 2020;00:1–14. DOI: https://doi.org/10.1080/08820139.2020.1837154
Gu LQ, Zhu W, Zhao SX, et al. Clinical associations of the genetic variants of CTLA-4, Tg, TSHR, PTPN-22, PTPN12 & FCRL3 in patients with graves’ disease. Clin Endocrinol 2010;72:248–55 DOI: https://doi.org/10.1111/j.1365-2265.2009.03617.x
Chabchoub G, Teixiera EP, Maalej A, et al. The R620W polymorphism of the protein tyrosine phosphatase 22 gene in autoimmune thyroid diseases & rheumatoid arthritis in the Tunisian population. Ann Human Biol 2009;36:342–9. DOI: https://doi.org/10.1080/03014460902817968
Nikitin Y, Ymar O, Maksimov V, et al. Association of PTPN-22 haplotypes with Hashimotos thyroiditis in population of Novosibirsk. Kliniceskaâ I Èksperimental’naâ Tireoidologiâ 2009;1:47–52. DOI: https://doi.org/10.14341/ket20095147-52
Kahles H, Amos-Lopez E, Lange B, et al. Sex-specific association of PTPN-22 1858T with type 1 diabetes but not with Hashimoto’s thyroiditis or Addison’s disease in the German population. Eur J Endocrinol 2005;153:895–9. DOI: https://doi.org/10.1530/eje.1.02035
Ban Y, Tozaki T, Taniyama M, et al. The codon 620 single nucleotide polymorphism of the protein tyrosine phosphatase-22 gene does not contribute to autoimmune thyroid disease susceptibility in the Japanese. Thyroid 2005;15:1115–18. DOI: https://doi.org/10.1089/thy.2005.15.1115
Smyth D, Cooper JD, Collins JE, et al. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN-22) with type 1 diabetes, & evidence for its role as a general autoimmunity locus. Diabetes 2004;53:3020–23. DOI: https://doi.org/10.2337/diabetes.53.11.3020
Abou El Ella, Soheir S, Mohammed ZS, et al. PTPN22 gene and IL2RA rs11594656, rs2104286 gene variants: additional insights of polygenic single-nucleotide polymorphisms’ pattern among Egyptian children with type 1 diabetes. Egyptian Pediatric Assoc Gazette 2021;69:35. DOI: https://doi.org/10.1186/s43054-021-00079-7
Huraib GB, Al Harthi F, Arfin M, et al. Association of Functional Polymorphism in Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Gene with Vitiligo. Biomark Insights 2020;31;15:1177271920903038. DOI: https://doi.org/10.1177/1177271920903038
Rajendiran KS, Rajappa M, Chandrashekar L, Thappa DM. Association of PTPN22 gene polymorphism with non-segmental vitiligo in South Indian Tamils. Postepy Dermatol Alergol 2018;35:280-85. DOI: https://doi.org/10.5114/ada.2018.76225
Pierce MJ, LaFranchi SH, Pinter JD. Characterization of thyroid abnormalities in a large cohort of children with down Syndrome. Hormone Res Paediatrics 2017;87:170–78. DOI: https://doi.org/10.1159/000457952
Tuysuz B, Beker DB.Thyroid dysfunction in children with down’s syndrome. Acta Paediatr 2001;90:1389–93. DOI: https://doi.org/10.1111/j.1651-2227.2001.tb01601.x
Gentile F, Conte M, Formisano S. Thyroglobulin as an autoantigen: What can we learn about immunopathogenicity from the association of antigenic properties with protein structure?. Immunology 2004;112:3–25. DOI: https://doi.org/10.1111/j.1365-2567.2004.01861.x
Karlsson B, Gustafsson J, Hedov G, et al. Thyroid dysfunction in down’s syndrome: relation to age and thyroid autoimmunity. Arch Dis Child 1998;79:242–5. DOI: https://doi.org/10.1136/adc.79.3.242
Pascanu I, Banescu C, Benedek T, et al. Thyroid dysfunction in children with down’s Syndrome. Acta Endocrinol (Bucharest, Rom.) 2009;5:85–92 DOI: https://doi.org/10.4183/aeb.2009.85
Luo L, Cai B, Liu F, et al. Association of protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T gene polymorphism with susceptibility to autoimmune thyroid diseases: A meta-analysis. Endocr J 2012;59:439–45. DOI: https://doi.org/10.1507/endocrj.EJ11-0381
Sam-Yellowe Tobili Y. Immunology: Overview and Laboratory. Clevelend,OH, USA. Springer Nature; 2021. DOI: https://doi.org/10.1007/978-3-030-64686-8
Bull MJ; Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics 2011;128:393-406. DOI: https://doi.org/10.1542/peds.2011-1605
Aversa T, Lombardo F, Valenzise M, et al. Peculiarities of autoimmune thyroid diseases in children with Turner or Downsyndrome: an overview. Ital J Ped 2015:41:1-5 DOI: https://doi.org/10.1186/s13052-015-0146-2
Zwaan MC, Reinhardt D, Hitzler J, Vyas P. Acute leukemias in children with Down syndrome. Pediatr Clin North Am 2008;55:53-70, x. DOI: https://doi.org/10.1016/j.pcl.2007.11.001
Patel H, Mansuri M, Singh M, et al. Association of Cytotoxic T- Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) genetic variants with autoimmune hypothyroidism. PLoS One 2016;11:e0149441. DOI: https://doi.org/10.1371/journal.pone.0149441
Jacobson EM, Tomer Y. The CD40, CTLA-4, thyroglobulin, TSH reseptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: Back to the future. J Autoimm 2007;28:85-98. DOI: https://doi.org/10.1016/j.jaut.2007.02.006
Copyright (c) 2023 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Downloads
Citations
