{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:51:59Z","timestamp":1788983519235,"version":"build-2803163510"},"reference-count":32,"publisher":"PAGEPress Publications","issue":"1","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatr Med Chir"],"abstract":"<jats:p>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\u00b117.3 months. The CT variant of PTPN-22 C1858T was observed in all subjects. The mean level of T3, FT4, and TSH were 1.59\u00b10.45 ng\/mL, 0.81\u00b10.57 ng\/mL, 0.22\u00b10.21 \u03bcU\/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.<\/jats:p>","DOI":"10.4081\/pmc.2023.283","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T14:38:27Z","timestamp":1677076707000},"source":"Crossref","is-referenced-by-count":3,"title":["Protein tyrosine phosphatase non-receptor type 22 C1858T gene polymorphism in children with down syndrome and autoimmune thyroid diseases"],"prefix":"10.4081","volume":"45","author":[{"given":"Muhammad","family":"Faizi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-9615","authenticated-orcid":false,"given":"Nur","family":"Rochmah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soetjipto","family":"Soetjipto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anang","family":"Endaryanto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5882-4251","authenticated-orcid":false,"given":"Sukmawati","family":"Basuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuni","family":"Hisbiyah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayi","family":"Kurnia Perwitasari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2549","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"1734","unstructured":"Al-Biltagi M. Down syndrome from epidemiologic point of view. EC Paediatrics 2015;82-91."},{"key":"1735","doi-asserted-by":"crossref","unstructured":"Ariani Y, Soeharso P, Sjarif DR. Genetic & genomic medicine in Indonesia. Molecular Genetics & Genomic Medicine 2017;5:103-9.","DOI":"10.1002\/mgg3.284"},{"key":"1736","doi-asserted-by":"crossref","unstructured":"Iughetti L, Predieri B, Buzzi P, et al. Ten-year longitudinal study of thyroid function in children with Down\u2019s syndrome. Horm Res Paediatr 2014; 82:113-21.","DOI":"10.1159\/000362450"},{"key":"1737","doi-asserted-by":"crossref","unstructured":"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":"10.1016\/j.ecl.2012.08.008"},{"key":"1738","doi-asserted-by":"crossref","unstructured":"Iughetti L, Lucaccioni L, Fugetto F, et al. Thyroid function in down syndrome, Expert Review of Endocrinol & Met 2015;10:525-32.","DOI":"10.1586\/17446651.2015.1063995"},{"key":"1739","unstructured":"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"},{"key":"1740","doi-asserted-by":"crossref","unstructured":"Vang T, Miletic AV, Bottini N, Mustelin T. Protein tyrosin phosphatase PTPN-22 in human autoimmunity. Autoimmunity 2007;40: 453-61.","DOI":"10.1080\/08916930701464897"},{"key":"1741","doi-asserted-by":"crossref","unstructured":"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":"10.1016\/j.febslet.2011.04.032"},{"key":"1742","doi-asserted-by":"crossref","unstructured":"World Medical Association. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull World Health Org 2001;79\u200e:373-374.","DOI":"10.4414\/fms.2001.04031"},{"key":"1743","doi-asserted-by":"crossref","unstructured":"Soghier L. Reference range values for pediatric care. 2nd ed. American Academy of Pediatric; 2019.","DOI":"10.1542\/9781610022811"},{"key":"1744","doi-asserted-by":"crossref","unstructured":"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\u201314.","DOI":"10.1080\/08820139.2020.1837154"},{"key":"1745","doi-asserted-by":"crossref","unstructured":"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\u2019 disease. Clin Endocrinol 2010;72:248\u201355","DOI":"10.1111\/j.1365-2265.2009.03617.x"},{"key":"1746","doi-asserted-by":"crossref","unstructured":"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\u20139.","DOI":"10.1080\/03014460902817968"},{"key":"1747","doi-asserted-by":"crossref","unstructured":"Nikitin Y, Ymar O, Maksimov V, et al. Association of PTPN-22 haplotypes with Hashimotos thyroiditis in population of Novosibirsk. Kliniceska\u00e2 I \u00c8ksperimental\u2019na\u00e2 Tireoidologi\u00e2 2009;1:47\u201352.","DOI":"10.14341\/ket20095147-52"},{"key":"1748","doi-asserted-by":"crossref","unstructured":"Kahles H, Amos-Lopez E, Lange B, et al. Sex-specific association of PTPN-22 1858T with type 1 diabetes but not with Hashimoto\u2019s thyroiditis or Addison\u2019s disease in the German population. Eur J Endocrinol 2005;153:895\u20139.","DOI":"10.1530\/eje.1.02035"},{"key":"1749","doi-asserted-by":"crossref","unstructured":"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\u201318.","DOI":"10.1089\/thy.2005.15.1115"},{"key":"1750","doi-asserted-by":"crossref","unstructured":"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\u201323.","DOI":"10.2337\/diabetes.53.11.3020"},{"key":"1751","doi-asserted-by":"crossref","unstructured":"Abou El Ella, Soheir S, Mohammed ZS, et al. PTPN22 gene and IL2RA rs11594656, rs2104286 gene variants: additional insights of polygenic single-nucleotide polymorphisms\u2019 pattern among Egyptian children with type 1 diabetes. Egyptian Pediatric Assoc Gazette 2021;69:35.","DOI":"10.1186\/s43054-021-00079-7"},{"key":"1752","doi-asserted-by":"crossref","unstructured":"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":"10.1177\/1177271920903038"},{"key":"1753","doi-asserted-by":"crossref","unstructured":"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":"10.5114\/ada.2018.76225"},{"key":"1754","doi-asserted-by":"crossref","unstructured":"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\u201378.","DOI":"10.1159\/000457952"},{"key":"1755","doi-asserted-by":"crossref","unstructured":"Tuysuz B, Beker DB.Thyroid dysfunction in children with down\u2019s syndrome. Acta Paediatr 2001;90:1389\u201393.","DOI":"10.1111\/j.1651-2227.2001.tb01601.x"},{"key":"1756","doi-asserted-by":"crossref","unstructured":"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\u201325.","DOI":"10.1111\/j.1365-2567.2004.01861.x"},{"key":"1757","doi-asserted-by":"crossref","unstructured":"Karlsson B, Gustafsson J, Hedov G, et al. Thyroid dysfunction in down\u2019s syndrome: relation to age and thyroid autoimmunity. Arch Dis Child 1998;79:242\u20135.","DOI":"10.1136\/adc.79.3.242"},{"key":"1758","doi-asserted-by":"crossref","unstructured":"Pascanu I, Banescu C, Benedek T, et al. Thyroid dysfunction in children with down\u2019s Syndrome. Acta Endocrinol (Bucharest, Rom.) 2009;5:85\u201392","DOI":"10.4183\/aeb.2009.85"},{"key":"1759","doi-asserted-by":"crossref","unstructured":"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\u201345.","DOI":"10.1507\/endocrj.EJ11-0381"},{"key":"1760","doi-asserted-by":"crossref","unstructured":"Sam-Yellowe Tobili Y. Immunology: Overview and Laboratory. Clevelend,OH, USA. Springer Nature; 2021.","DOI":"10.1007\/978-3-030-64686-8"},{"key":"1761","doi-asserted-by":"crossref","unstructured":"Bull MJ; Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics 2011;128:393-406.","DOI":"10.1542\/peds.2011-1605"},{"key":"1762","doi-asserted-by":"crossref","unstructured":"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":"10.1186\/s13052-015-0146-2"},{"key":"1763","doi-asserted-by":"crossref","unstructured":"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":"10.1016\/j.pcl.2007.11.001"},{"key":"1764","doi-asserted-by":"crossref","unstructured":"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":"10.1371\/journal.pone.0149441"},{"key":"1765","doi-asserted-by":"crossref","unstructured":"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":"10.1016\/j.jaut.2007.02.006"}],"container-title":["La Pediatria Medica e Chirurgica"],"original-title":[],"link":[{"URL":"https:\/\/www.pediatrmedchir.org\/pmc\/article\/download\/283\/334","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.pediatrmedchir.org\/pmc\/article\/download\/283\/334","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T14:38:36Z","timestamp":1677076716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.pediatrmedchir.org\/pmc\/article\/view\/283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,22]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,2,22]]}},"URL":"https:\/\/doi.org\/10.4081\/pmc.2023.283","relation":{},"ISSN":["2420-7748","0391-5387"],"issn-type":[{"value":"2420-7748","type":"electronic"},{"value":"0391-5387","type":"print"}],"subject":[],"published":{"date-parts":[[2023,2,22]]}}}