The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes

BMC Med Genet. 2011 Mar 23;12:41. doi: 10.1186/1471-2350-12-41.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood
  • C-Peptide / blood
  • Child
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetic Ketoacidosis / etiology
  • Diabetic Ketoacidosis / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Proinsulin / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics*
  • Regression Analysis
  • Time Factors

Substances

  • Autoantibodies
  • C-Peptide
  • Proinsulin
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22