DNA hypermethylation of PTPN22 gene promoter in children and adolescents with Hashimoto thyroiditis.

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.

Common VDR polymorphisms and idiopathic short stature in children from northern Greece.

BACKGROUND: A Vitamin D Receptor gene (VDR) polymorphism, rs10735810 (Fok1), has been associated in the past with idiopathic short stature (ISS) in a linkage study. We have investigated the association of the same, as well as a different polymorphism in the same gene [rs731236 (Taq1)] with ISS, in an independent study in Greek children. METHODS: The VDR rs10735810 (Fok1) and rs731236 (Taq1) polymorphisms were genotyped in a group of ISS children (n= 47) and an age and sex-matched group of normal height children (n= 60) from northern Greece. Genotyping was accomplished through established PCR-RFLP methods. RESULTS: An association trend of rs10735810 with ISS was observed, with the TT (ff) genotype being apparently underrepresented among ISS children compared to controls (p= 0.076; OR= 0.165, 95% CI= 0.025-1.094). CONCLUSIONS: The above results, together with recent evidence related to the functionality of the rs10735810 polymorphism, cannot exclude an involvement of VDR in the pathogenesis of ISS. Hippokratia 2015, 19 (1): 25-29.

Apelin and G212A apelin receptor gene polymorphism in obese and diabese youth.

OBJECTIVE: The apelinergic system has been previously described to participate in fluid homeostasis, cardiac contractility, blood pressure and neo-vascularization. The role of apelin in obesity and glucose metabolism has also lately gained interest; however, it still remains obscure. This study aimed to assess serum apelin levels in obese youngsters and to investigate any possible association with the G212A polymorphism of the apelin receptor (APLNR) gene. METHODS: Ninety obese individuals and 90 matched for age and gender lean controls were included. Anthropometric measurements, data of glucose metabolism, including an oral glucose tolerance test, and serum apelin levels were obtained. The presence of the G212A polymorphism of the APLNR gene was also analyzed in the obese group. RESULTS: Obese participants had significantly lower serum apelin levels as compared with controls (P = 0.011). After being grouped according to their status of glucose metabolism, only obese subjects with impaired glucose metabolism (diabese) exhibited lower apelin levels as compared with controls. The presence of the G212A polymorphism did not differ from the HapMap-reported frequencies in Caucasians (GG = 53.3%/GA = 38.9%/ΑΑ = 7.8% vs. GG = 46.9%/GA = 39.8%/ΑΑ = 13.3%, P = 0.232). The GG and GA obese subgroups had significantly lower apelin levels as compared with the AA group (P = 0.013 and P = 0.016, respectively). CONCLUSION: Obese (especially diabese) youngsters demonstrated lower serum apelin levels; the G212A polymorphism of the APLNR gene was found to exert a favourable effect on circulating apelin levels in childhood obesity.

Two-year cyclic infusion of pamidronate improves bone mass density and eliminates risk of fractures in a girl with osteoporosis due to Hajdu-Cheney syndrome.

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.