The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes
| Autor: | Nielsen, L.B., Pörksen, S., Andersen, M.L., Fredheim, S., Svensson, J., Hougaard, P., Vanelli, M., Åman, J., Mortensen, H.B., Hansen, L., De Beaufort, Carine |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Time Factors endocrine system diseases type 1 diabetes medicine.medical_treatment Cohort Studies chemistry.chemical_compound 0302 clinical medicine Genetics(clinical) Child Genetics (clinical) Multidisciplinary general & others [D99] [Human health sciences] Proinsulin 0303 health sciences C-Peptide C-peptide PTPN22 Regression Analysis Female Research Article lcsh:Internal medicine medicine.medical_specialty proinsulin lcsh:QH426-470 Diabetic ketoacidosis Multidisciplinaire généralités & autres [D99] [Sciences de la santé humaine] C1858T 030209 endocrinology & metabolism Enzyme-Linked Immunosorbent Assay Biology Polymorphism Single Nucleotide Diabetic Ketoacidosis 03 medical and health sciences Internal medicine Diabetes mellitus Genetics medicine Humans Genetic Predisposition to Disease lcsh:RC31-1245 030304 developmental biology Glycemic Autoantibodies Type 1 diabetes childhood diabetes Insulin Protein Tyrosine Phosphatase Non-Receptor Type 22 medicine.disease lcsh:Genetics Endocrinology Diabetes Mellitus Type 1 chemistry |
| Zdroj: | BMC Medical Genetics, 12(41). BioMed Central (2011). BMC Medical Genetics Nielsen, L B, Porksen, S, Andersen, M L M, Fredheim, S, Svensson, J, Hougaard, P, Vanelli, M, Aman, J, Mortensen, H B, Hansen, L & Hvidoere Study Grp, C 2011, ' The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes ', B M C Medical Genetics, vol. 12, pp. 41 . https://doi.org/10.1186/1471-2350-12-41 BMC Medical Genetics, Vol 12, Iss 1, p 41 (2011) |
| Popis: | Background The protein tyrosine phosphatase nonreceptor type 2 (PTPN22) has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c), glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA) and diabetes-related autoantibodies (IA-2A, GADA, ICA, ZnT8Ab) in children during the first year after diagnosis of type 1 diabetes. Methods The C1858T variant was genotyped in an international cohort of children (n = 257 patients) with newly diagnosed type 1 diabetes during 12 months after onset. We investigated the association of this variant with liquid-meal stimulated beta-cell function (proinsulin and C-peptide) and antibody status 1, 6 and 12 months after onset. In addition HbA1c and daily insulin requirements were determined 1, 3, 6, 9 and 12 months after diagnosis. DKA was defined at disease onset. Results A repeated measurement model of all time points showed the stimulated proinsulin level is significantly higher (22%, p = 0.03) for the T allele carriers the first year after onset. We also found a significant positive association between proinsulin and IA levels (est.: 1.12, p = 0.002), which did not influence the association between PTPN22 and proinsulin (est.: 1.28, p = 0.03). Conclusions The T allele of the C1858T variant is positively associated with proinsulin levels during the first 12 months in newly diagnosed type 1 diabetes children. |
| Databáze: | OpenAIRE |
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