ABSTRACT
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Biomarkers/analysis , DNA Methylation , Genetic Predisposition to Disease , Hashimoto Disease/diagnosis , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Adolescent , Case-Control Studies , Child , Female , Follow-Up Studies , Greece/epidemiology , Hashimoto Disease/epidemiology , Hashimoto Disease/genetics , Humans , Male , PrognosisABSTRACT
Hajdu-Cheney syndrome (HCS) is a rare disorder principally characterized by acro-osteolysis, distinctive craniofacial and skull changes, dental anomalies and short stature. A common finding in HCS patients is secondary osteoporosis that progresses over time and contributes to various skeletal problems, especially fractures. Although autosomal dominant inheritance has been documented in several families, sporadic (non-familial) cases have also been reported. Here, a case of a 9-year-old girl with familial HCS and multiple spinal fractures, who has been effectively treated with pamidronate, is presented. This is the first report of a beneficial effect of intravenous bisphosphonate administration on a child with HCS-related osteoporosis.
