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. 2011 Mar 23:12:41.
doi: 10.1186/1471-2350-12-41.

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

Lotte B Nielsen  1 , Sven Pörksen, Marie Louise M Andersen, Siri Fredheim, Jannet Svensson, Philip Hougaard, Maurizio Vanelli, Jan Åman, Henrik B Mortensen, Lars Hansen; Hvidoere Study Group on Childhood Diabetes
Collaborators, Affiliations

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

Lotte B Nielsen et al. BMC Med Genet. .

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.

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Figures

Figure 1
Figure 1
Stimulated C-peptide and proinsulin over time according to PTPN22 genotypes. The association of stimulated C-peptide (A.) and proinsulin (B.) level 1, 6 and 12 months after disease onset by PTPN22 genotype (homozygous+heterozygous (CT+TT) (n = 71) carriers of the variant versus wildtype (CC) (n = 186)). Mean values (pmol/l) ± SEM.
Figure 2
Figure 2
Insulin antibodies over time according to PTPN22 genotypes. Distribution of insulin antibodies (IA) by PTPN22 genotype ((CT+TT) (n = 71) carriers of the variant versus wildtype (CC) (n = 186)) 12 months after disease onset. Mean values (pmol/l) ± SEM.
See this image and copyright information in PMC

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