Protein tyrosine phosphatase non-receptor type 22 C1858T gene polymorphism in children with Down syndrome and autoimmune thyroid diseases


Submitted: 19 January 2022
Accepted: 28 December 2022
Published: 22 February 2023
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Authors

  • Muhammad Faizi Department of Child Health, Faculty of Medicine, Dr. Soetomo General Hospital, Universitas Airlangga, Surabaya, East Java, Indonesia.
  • Nur Rochmah Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia. https://orcid.org/0000-0002-9626-9615
  • Soetjipto Soetjipto Department of Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia; Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia.
  • Anang Endaryanto Department of Child Health, Faculty of Medicine, Dr. Soetomo General Hospital, Universitas Airlangga, Surabaya, East Java, Indonesia; Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia.
  • Sukmawati Basuki Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia; Department of Parasitology, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java,, Indonesia. https://orcid.org/0000-0002-5882-4251
  • Yuni Hisbiyah Department of Child Health, Faculty of Medicine, Dr. Soetomo General Hospital, Universitas Airlangga, Surabaya, East Java, Indonesia; Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia.
  • Rayi Kurnia Perwitasari Department of Child Health, Faculty of Medicine, Dr. Soetomo General Hospital, Universitas Airlangga, Surabaya, East Java, Indonesia.

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

Faizi, M., Rochmah, N., Soetjipto, S., Endaryanto, A., Basuki, S., Hisbiyah, Y., & Kurnia Perwitasari, R. (2023). Protein tyrosine phosphatase non-receptor type 22 C1858T gene polymorphism in children with Down syndrome and autoimmune thyroid diseases. La Pediatria Medica E Chirurgica, 45(1). https://doi.org/10.4081/pmc.2023.283

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