DNA hypermethylation of PTPN22 gene promoter in children and adolescents with Hashimoto thyroiditis.
Adolescent
Biomarkers
/ analysis
Case-Control Studies
Child
DNA Methylation
Female
Follow-Up Studies
Genetic Predisposition to Disease
Greece
/ epidemiology
Hashimoto Disease
/ diagnosis
Humans
Male
Polymorphism, Single Nucleotide
Prognosis
Promoter Regions, Genetic
Protein Tyrosine Phosphatase, Non-Receptor Type 22
/ genetics
Autoimmune thyroid disease
Children and adolescents
DNA methylation
Hashimoto thyroiditis
Melting curve analysis
PTPN22
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
13
03
2020
accepted:
30
10
2020
pubmed:
23
3
2021
medline:
19
1
2022
entrez:
22
3
2021
Statut:
ppublish
Résumé
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is an inhibitor of T-cell activation, regulating intracellular signal transduction and thereby being implicated in the pathogenesis of autoimmune thyroid disease (AITD). The exact molecular mechanisms have not been fully elucidated. The aim of the present study was to quantitate DNA methylation within the PTPN22 gene promoter in children and adolescents with AITD and healthy controls. 60 Patients with Hashimoto thyroiditis (HT), 25 patients with HT and type 1 diabetes (HT + T1D), 9 patients with Graves' disease (GD) and 55 healthy controls without any individual or family history of autoimmune disease were enrolled. Whole blood DNA extraction, DNA modification using sodium bisulfate and quantification of DNA methylation in the PTPN22 gene promoter, based on melting curve analysis of the selected DNA fragment using a Real-Time PCR assay, were implemented. DNA methylation in the PTPN22 gene promoter was found to be significantly higher in HT patients (39.9 ± 3.1%) in comparison with other study groups (20.3 ± 2.4% for HT + T1D, 32.6 ± 7.8% for GD, 27.1 ± 2.4% for controls, p < 0.001). PTPN22 gene promoter DNA methylation was also associated marginally with thyroid autoimmunity in general (p = 0.059), as well as considerably with thyroid volume (p = 0.004) and the presence of goiter (p = 0.001) but not thyroid function tests. This study demonstrates for the first time that a relationship between autoimmune thyroiditis and PTPN22 gene promoter DNA methylation state is present, thus proposing another possible etiological association between thyroiditis and abnormalities of PTPN22 function. Further expression studies are required to confirm these findings.
Identifiants
pubmed: 33751486
doi: 10.1007/s40618-020-01463-7
pii: 10.1007/s40618-020-01463-7
doi:
Substances chimiques
Biomarkers
0
PTPN22 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 22
EC 3.1.3.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2131-2138Subventions
Organisme : Research Committee, Aristotle University of Thessaloniki
ID : 89650
Informations de copyright
© 2020. Italian Society of Endocrinology (SIE).
Références
Coppedè F (2017) Epigenetics and autoimmune thyroid diseases. Front Endocrinol (Lausanne) 8:149. https://doi.org/10.3389/fendo.2017.00149
doi: 10.3389/fendo.2017.00149
Effraimidis G, Wiersinga WM (2014) Mechanisms in endocrinology: autoimmune thyroid disease: old and new players. Eur J Endocrinol 170(6):R241–R252. https://doi.org/10.1530/EJE-14-0047
doi: 10.1530/EJE-14-0047
pubmed: 24609834
Tomer Y (2014) Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics. Annu Rev Pathol 9:147–156. https://doi.org/10.1146/annurev-pathol-012513-104713
doi: 10.1146/annurev-pathol-012513-104713
pubmed: 24460189
pmcid: 4128637
Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13(7):484–492. https://doi.org/10.1038/nrg3230
doi: 10.1038/nrg3230
pubmed: 22641018
Fournier A, Sasai N, Nakao M, Defossez PA (2012) The role of methyl-binding proteins in chromatin organization and epigenome maintenance. Brief Funct Genomics 11(3):251–264. https://doi.org/10.1093/bfgp/elr040
doi: 10.1093/bfgp/elr040
pubmed: 22184333
Cohen S, Dadi H, Shaoul E, Sharfe N, Roifman CM (1999) Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp. Blood 93(6):2013–2024
doi: 10.1182/blood.V93.6.2013.406k25_2013_2024
Mustelin T, Bottini N, Stanford SM (2019) The contribution of PTPN22 to rheumatic disease. Arthritis Rheumatol 71(4):486–495. https://doi.org/10.1002/art.40790
doi: 10.1002/art.40790
pubmed: 30507064
pmcid: 6438733
Burn GL, Svensson L, Sanchez-Blanco C, Saini M, Cope AP (2011) Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett 585(23):3689–3698. https://doi.org/10.1016/j.febslet.2011.04.032
doi: 10.1016/j.febslet.2011.04.032
pubmed: 21515266
Simera I, Moher D, Hoey J, Schulz KF, Altman DG (2010) A catalogue of reporting guidelines for health research. Eur J Clin Investig 40(1):35–53. https://doi.org/10.1111/j.1365-2362.2009.02234.x
doi: 10.1111/j.1365-2362.2009.02234.x
Caturegli P, De Remigis A, Rose NR (2014) Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev 13(4–5):391–397. https://doi.org/10.1016/j.autrev.2014.01.007
doi: 10.1016/j.autrev.2014.01.007
pubmed: 24434360
Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P, Craig ME (2018) ISPAD Clinical Practice Consensus Guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 19(Suppl 27):7–19. https://doi.org/10.1111/pedi.12773
doi: 10.1111/pedi.12773
pubmed: 30226024
pmcid: 7521365
Alisch RS, Barwick BG, Chopra P, Myrick LK, Satten GA, Conneely KN, Warren ST (2012) Age-associated DNA methylation in pediatric populations. Genome Res 22(4):623–632. https://doi.org/10.1101/gr.125187.111
doi: 10.1101/gr.125187.111
pubmed: 22300631
pmcid: 3317145
The Children’s Hospital of Philadelphia: Research Institute Pediatric Z-Score Calculator. https://zscore.research.chop.edu/ . Accessed 8 March 2020
Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC (2007) Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects. Atherosclerosis 191(1):63–72. https://doi.org/10.1016/j.atherosclerosis.2006.05.032
doi: 10.1016/j.atherosclerosis.2006.05.032
pubmed: 16806233
Wettinger SB, Doggen CJ, Spek CA, Rosendaal FR, Reitsma PH (2005) High throughput mRNA profiling highlights associations between myocardial infarction and aberrant expression of inflammatory molecules in blood cells. Blood 105(5):2000–2006. https://doi.org/10.1182/blood-2004-08-3283
doi: 10.1182/blood-2004-08-3283
pubmed: 15522960
Smith E, Jones ME, Drew PA (2009) Quantitation of DNA methylation by melt curve analysis. BMC Cancer 9:123. https://doi.org/10.1186/1471-2407-9-123
doi: 10.1186/1471-2407-9-123
pubmed: 19393074
pmcid: 2679043
Arroyo-Jousse V, Garcia-Diaz DF, Codner E, Pérez-Bravo F (2016) Epigenetics in type 1 diabetes: TNFa gene promoter methylation status in Chilean patients with type 1 diabetes mellitus. Br J Nutr 116(11):1861–1868. https://doi.org/10.1017/S0007114516003846
doi: 10.1017/S0007114516003846
pubmed: 27890035
Kyrgios I, Fragou A, Kotanidou EP, Mouzaki K, Efraimidou S, Tzimagiorgis G, Galli-Tsinopoulou A (2020) DNA methylation analysis within the IL2RA gene promoter in youth with autoimmune thyroid disease. Eur J Clin Investig 50(3):e13199. https://doi.org/10.1111/eci.13199
doi: 10.1111/eci.13199
The Li Lab MethPrimer. https://www.urogene.org/methprimer/ . Accessed 8 March 2020
Li LC, Dahiya R (2002) MethPrimer: designing primers for methylation PCRs. Bioinformatics 18(11):1427–1431. https://doi.org/10.1093/bioinformatics/18.11.1427
doi: 10.1093/bioinformatics/18.11.1427
pubmed: 12424112
The UCSC Genomics Institute Genome Browser. https://genome.ucsc.edu/index.html . Accessed 8 March 2020
Kurdyukov S, Bullock M (2016) DNA methylation analysis: choosing the right method. Biology (Basel). https://doi.org/10.3390/biology5010003
doi: 10.3390/biology5010003
Lorente A, Mueller W, Urdangarín E, Lázcoz P, von Deimling A, Castresana JS (2008) Detection of methylation in promoter sequences by melting curve analysis-based semiquantitative real time PCR. BMC Cancer 8:61. https://doi.org/10.1186/1471-2407-8-61
doi: 10.1186/1471-2407-8-61
pubmed: 18298842
pmcid: 2266933
Wojdacz TK, Dobrovic A (2007) Methylation-sensitive high resolution melting (MS-HRM): a new approach for sensitive and high-throughput assessment of methylation. Nucleic Acids Res 35(6):e41. https://doi.org/10.1093/nar/gkm013
doi: 10.1093/nar/gkm013
pubmed: 17289753
pmcid: 1874596
Amornpisutt R, Sriraksa R, Limpaiboon T (2012) Validation of methylation-sensitive high resolution melting for the detection of DNA methylation in cholangiocarcinoma. Clin Biochem 45(13–14):1092–1094. https://doi.org/10.1016/j.clinbiochem.2012.04.027
doi: 10.1016/j.clinbiochem.2012.04.027
pubmed: 22569599
The NCBI BLAST. https://blast.ncbi.nlm.nih.gov . Accessed 8 March 2020
Dell RB, Holleran S, Ramakrishnan R (2002) Sample size determination. ILAR J 43(4):207–213. https://doi.org/10.1093/ilar.43.4.207
doi: 10.1093/ilar.43.4.207
pubmed: 12391396
Center for Biomathematics Biomath. https://www.biomath.info . Accessed 8 March 2020
Brčić L, Barić A, Gračan S, Brekalo M, Kaličanin D, Gunjača I, Torlak Lovrić V, Tokić S, Radman M, Škrabić V, Miljković A, Kolčić I, Štefanić M, Glavaš-Obrovac L, Lessel D, Polašek O, Zemunik T, Barbalić M, Punda A, Boraska Perica V (2019) Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis. J Endocrinol Investig 42(5):567–576. https://doi.org/10.1007/s40618-018-0955-4
doi: 10.1007/s40618-018-0955-4
Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, Eisenbarth GS, Comings D, Mustelin T (2004) A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 36(4):337–338. https://doi.org/10.1038/ng1323
doi: 10.1038/ng1323
pubmed: 15004560
Dultz G, Matheis N, Dittmar M, Röhrig B, Bender K, Kahaly GJ (2009) The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes. Thyroid 19(2):143–148. https://doi.org/10.1089/thy.2008.0301
doi: 10.1089/thy.2008.0301
pubmed: 19090780
Giza S, Goulas A, Gbandi E, Effraimidou S, Papadopoulou-Alataki E, Eboriadou M, Galli-Tsinopoulou A (2013) The role of PTPN22 C1858T gene polymorphism in diabetes mellitus type 1: first evaluation in Greek children and adolescents. Biomed Res Int 2013:721604. https://doi.org/10.1155/2013/721604
doi: 10.1155/2013/721604
pubmed: 23936838
pmcid: 3727122
Velaga MR, Wilson V, Jennings CE, Owen CJ, Herington S, Donaldson PT, Ball SG, James RA, Quinton R, Perros P, Pearce SH (2004) The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves’ disease. J Clin Endocrinol Metab 89(11):5862–5865. https://doi.org/10.1210/jc.2004-1108
doi: 10.1210/jc.2004-1108
pubmed: 15531553
Heward JM, Brand OJ, Barrett JC, Carr-Smith JD, Franklyn JA, Gough SC (2007) Association of PTPN22 haplotypes with Graves’ disease. J Clin Endocrinol Metab 92(2):685–690. https://doi.org/10.1210/jc.2006-2064
doi: 10.1210/jc.2006-2064
pubmed: 17148556
Lee YH, Rho YH, Choi SJ, Ji JD, Song GG, Nath SK, Harley JB (2007) The PTPN22 C1858T functional polymorphism and autoimmune diseases—a meta-analysis. Rheumatology (Oxf) 46(1):49–56. https://doi.org/10.1093/rheumatology/kel170
doi: 10.1093/rheumatology/kel170
Lefvert AK, Zhao Y, Ramanujam R, Yu S, Pirskanen R, Hammarstrom L (2008) PTPN22 R620W promotes production of anti-AChR autoantibodies and IL-2 in myasthenia gravis. J Neuroimmunol 197(2):110–113. https://doi.org/10.1016/j.jneuroim.2008.04.004
doi: 10.1016/j.jneuroim.2008.04.004
pubmed: 18533277
Vang T, Congia M, Macis MD, Musumeci L, Orrú V, Zavattari P, Nika K, Tautz L, Taskén K, Cucca F, Mustelin T, Bottini N (2005) Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 37(12):1317–1319. https://doi.org/10.1038/ng1673
doi: 10.1038/ng1673
pubmed: 16273109
Cai TT, Muhali FS, Song RH, Qin Q, Wang X, Shi LF, Jiang WJ, Xiao L, Li DF, Zhang JA (2015) Genome-wide DNA methylation analysis in Graves’ disease. Genomics 105(4):204–210. https://doi.org/10.1016/j.ygeno.2015.01.001
doi: 10.1016/j.ygeno.2015.01.001
pubmed: 25617714
Limbach M, Saare M, Tserel L, Kisand K, Eglit T, Sauer S, Axelsson T, Syvänen AC, Metspalu A, Milani L, Peterson P (2016) Epigenetic profiling in CD4
doi: 10.1016/j.jaut.2015.09.006
pubmed: 26459776
Chandra A, Senapati S, Roy S, Chatterjee G, Chatterjee R (2018) Epigenome-wide DNA methylation regulates cardinal pathological features of psoriasis. Clin Epigenet 10(1):108. https://doi.org/10.1186/s13148-018-0541-9
doi: 10.1186/s13148-018-0541-9
Shalaby SM, Mackawy AMH, Atef DM, Atef RM, Saeed J (2019) Promoter methylation and expression of intercellular adhesion molecule 1 gene in blood of autoimmune thyroiditis patients. Mol Biol Rep 46(5):5345–5353. https://doi.org/10.1007/s11033-019-04990-6
doi: 10.1007/s11033-019-04990-6
pubmed: 31359380
Liu T, Sun J, Wang Z, Yang W, Zhang H, Fan C, Shan Z, Teng W (2017) Changes in the DNA methylation and hydroxymethylation status of the intercellular adhesion molecule 1 gene promoter in thyrocytes from autoimmune thyroiditis patients. Thyroid 27(6):838–845. https://doi.org/10.1089/thy.2016.0576
doi: 10.1089/thy.2016.0576
pubmed: 28388873
Morita E, Watanabe M, Inoue N, Hashimoto H, Haga E, Hidaka Y, Iwatani Y (2018) Methylation levels of the TNFA gene are different between Graves’ and Hashimoto’s diseases and influenced by the TNFA polymorphism. Autoimmunity 51(3):118–125. https://doi.org/10.1080/08916934.2018.1448078
doi: 10.1080/08916934.2018.1448078
pubmed: 29526119
Hashimoto H, Watanabe M, Inoue N, Hirai N, Haga E, Kinoshita R, Hidaka Y, Iwatani Y (2019) Association of IFNG gene methylation in peripheral blood cells with the development and prognosis of autoimmune thyroid diseases. Cytokine 123:154770. https://doi.org/10.1016/j.cyto.2019.154770
doi: 10.1016/j.cyto.2019.154770
pubmed: 31279175
Xin Z, Hua L, Shi TT, Tuo X, Yang FY, Li Y, Cao X, Yang JK (2018) A genome-wide DNA methylation analysis in peripheral blood from patients identifies risk loci associated with Graves’ orbitopathy. J Endocrinol Investig 41(6):719–727. https://doi.org/10.1007/s40618-017-0796-6
doi: 10.1007/s40618-017-0796-6
Wojciechowska-Durczynska K, Krawczyk-Rusiecka K, Zygmunt A, Stawerska R, Lewinski A (2016) In children with autoimmune thyroiditis CTLA4 and FCRL3 genes—but not PTPN22—are overexpressed when compared to adults. Neuroendocrinol Lett 37(1):65–69
pubmed: 26994388
Tokić S, Štefanić M, Glavaš-Obrovac L, Kishore A, Navratilova Z, Petrek M (2018) miR-29a-3p/T-bet regulatory circuit is altered in T cells of patients with Hashimoto’s thyroiditis. Front Endocrinol (Lausanne) 9:264. https://doi.org/10.3389/fendo.2018.00264
doi: 10.3389/fendo.2018.00264